Week 2 Flashcards
What are the 2 phases of pain and what fibres are responsible?
Quick and sharp - Aδ
Slow and dull - C
What sensory receptors are associated with Aα fibres?
Proprioceptors of skeletal muscle
What sensory receptors are associated with Aβ fibres?
Mechanoreceptors of skin
What sensory receptors are associated with Aδ fibres?
Pain and temperature
What sensory receptors are associated with C fibres?
Pain, temperature and itch
What is nociceptive pain?
Normal pain elicited only when a noxious stimulus which threatens to damage tissue is evoked
Protective/adaptive
High threshold, limited duration
Transmitted by Aδ and C fibres
What is chronic/clinical pain?
Evoked or spontaneous sustained sensory abnormality/peripheral pathology - stimulated by normally innocuous sensation
Maladaptive
Transmitted by Aβ, Aδ and C fibres
What is allodynia?
Normally innocuous stimuli perceived as noxious
What do hair follicle afferent receptors respond to?
Gentle brushing
What is dermatographia?
Condition in which light scratching of the skin causes intense reddening and raising - skin writing
What does the white reaction and triple response demonstrate?
Local effects of mild tissue damage
What is the white reaction and triple response?
White reaction - initial area of blanching on either side of scratch
Triple response - red reaction, wheal and flare
What is the red reaction, wheal and flare of the triple response?
Red reaction - red line at site of injury due to direct vasodilation mediated by histamine (primary hyperalgesia)
Wheal - slight oedema at site around red reaction, mediated by histamine
Flare - surrounding ill-defined erythema due to axon reflex (secondary hyperalgesia)
What mediators are released when tissue is damaged and where from?
Tissue damage - K+, prostaglandins
Plasma - bradykinin
Platelets - 5-HT
What mediators are released from axons at the site of tissue damage?
Substance P and CGRP which activate mast cells to release histamine
What role do substance P and CGRP play in tissue damage?
Substance P - plasma extravasation, oedema, bradykinin release
CGRP - vasodilation
What is ischaemic pain?
Pain associated with inadequate blood (and therefore oxygen) supply to active tissues (e.g. angina)
Where does referred pain from the heart radiate?
Left shoulder and arm
What laminae do Aδ and C-fibres terminate at in the spinal cord?
Laminae I and II
What laminae do Aβ (cutaneous) fibres terminate at in the spinal cord?
Laminae III-V
How does the supraspinal loop contribute to the modulation of nociceptive afferent input?
Serotonergic and
noradrenergic descending
projections from the periaqueductal grey matter
and medullary raphe nuclei directly inhibit projection of neurons and/or activate enkephalin containing interneurons to reduce nociceptive activity
What are the 2 explanations for how TENS machines work?
1 - stimulating large diameter axons of other sensory receptors, a jamming effect is created in the dorsal horn of the spinal cord (pain perception reduced/abolished by interference with pathway transmission)
2 - stimulation releases endorphins from the brainstem which activates descending pathways and suppresses pain pathway
What conditions are TENS machines used for?
RA, sciatica, sports injuries, MS, phantom-limb pain
What results should a cold-pressor test give?
Increased HR and BP as the sympathetic system is activated; will plateau/decrease eventually as parasympathetic is activated to maintain homeostasis
What are the 3 families of endogenous opioid peptides?
Enkephalins
POMC
Dynorphins
What are the 3 types of opioid receptor?
Mu, delta, kappa
Describe a monosynaptic reflex
Involves a proprioceptive afferent (Ia) and motor neuron
Passive stretch of quadriceps muscle activates Ia afferents via muscle spindle → synapse in spinal cord → activation of motor neuron to cause muscle contraction at motor end plate
What segmental variation is seen in the spinal cord?
Enlarged at cervial (C5-T1) and lumbar (L2-S3) levels due to innervation of limbs
What is the ventral horn composed of?
Origin of motor neurons for skeletal muscle
What is the dorsal horn composed of?
Terminations of incoming sensory fibres
What are the divisions of grey matter?
Dorsal horn, intermediate area, ventral horn
What are the divisions of white matter?
Dorsal, lateral and ventral columns
What is the filum terminalae composed of?
Thin strand of pia mater
What does the dura mater merge with to cover spinal nerves?
Epineurium (connective tissue)
What is found in the extra/epidural space?
Fat, venous plexus
At what point is the spinal cord continuous with the brainstem?
At the level of the foramen magnum
What is the lumbar cistern?
Sac of dura mater which encloses the cauda equina
What are the characteristic features of a lumbar vertebra?
Large body, small vertebral canal, small transverse processes without facets
What are the characteristic features of a cervical vertebra?
Foramen transversarium, bifid spinous process, large vertebral canal
What are the characteristic features of a thoracic vertebra?
Transverse processes articulate with ribs
What are the 5 groups of branches of the facial nerve (CN 7)?
Temporal Zygomatic Buccal Marginal mandibular Cervical
What are the main arteries of the face?
Superficial temporal artery (branch of external carotid) Facial artery (gives of superior and anterior labial branches to the lips)
Why is the facial artery tortuous?
Allows blood flow to be maintained when mandible is moved
What is the main vein of the face?
Facial vein (joins internal jugular vein)
What overlies the masseter muscle in the face?
Parotid gland
Where does the parotid duct open?
Next to the crown of the 2nd upper molar
How can pain manifest from the parotid gland?
Thick capsule surrounding the gland maintains pressure which can cause pain in conditions such as mumps
Describe the path the facial nerve (CN 7) takes to reach the face
Emerges from the base of the skull at the stylomastoid foramen and branches within the parotid gland
What muscle does the cervical branch of the facial nerve innervate?
Platysma
In which week of gestation does the CNS begin to develop?
Week 3
What does the ectoderm germ layer form?
CNS, PNS, sensory epithelium of the ear/nose/eye, epidermis, hair and nails, subcutaneous/mammary/pituitary glands, tooth enamel
Where does the notochord extend from and how does this occur?
From the primitive node at the end of the primitive streak
Hypoblast cells are displaced by movement of epiblast cells (endoderm replaced hypoblast)
What are the stages of notochord development?
Axial process → notochordal process → notochord
How is the notochord involved in neurulation?
Notochord has an inductive relationship with the overlying ectoderm - its appearance causes the ectoderm to thicken
From which germ layer is the notochord derived?
Mesoderm
Briefly describe the process of neurulation
Notochord → ectoderm thickening → neural plate made of neuroectoderm → plate edges elevate to form neural folds → depressed mid-region forms neural groove → fusion of folds results in neural tube
What factors does bending of the neural plate depend on?
Intrinsic - cytoskeleton, stage of cell cycle
Extrinsic - adhesion points
What are neural crest cells?
Cells which remain at the top of the neural tube on fusion of the neural folds; give rise to range of cell types (e.g. glia)
What hinge points are involved in neural tube formation?
Median hinge point - neural groove area
Dorsolateral hinge points - on either side where the neural folds are
How do hinge points contribute to neural tube closure?
Cells in these areas decrease in height and become wedge-shaped which allows the neuroectoderm to bend
What lies on either side of the closed neural tube?
Paraxial mesoderm (somites) Then intermediate and lateral plate mesoderm more laterally
What signalling molecules are involved in induction of the neural plate?
FGF and BMP4
What is the role of chordin and noggin in neurulation?
Inhibit BMP4 which pushes tissue towards a neural phenotype
What switch in cell type occurs in the neural plate to allow fusion of the neural tube?
Switch from E-cadherin to N-cadherin expression
What happens to the neural crest cells after neurulation?
Undergo an epithelial to mesenchymal transition
What is the molecular difference between epithelial and mesenchymal cells?
Epithelial cells have high E-cadherin expression
Mesenchymal cells have high N-cadherin expression
What do neural crest cells form?
Trunk region - melanocytes, hair follicles, dorsal root ganglia, sensory ganglia, sympathetic neurons, Schwann cells, adrenal medulla
Cranial region - craniofacial skeleton, neurons, ganglia, glia, melanocytes
What is the basal lamina and what is its importance in development?
Layer of extracellular matrix secreted by epithelial cell
In the myotome, allows cells to migrate between the neural tube and the rest of the embryo
What disorders can occur when neural crest cell migration is disrupted?
Treacher Collins syndrome - underdevelopment of facial bones and ears; TCOF 1 gene mutation
Di George syndrome - cleft palate, abnormal facies, cardiac problems; 22q11.2 gene deletion
At what level does the neural tube begin to close and in what direction does it occur?
Starts in cervical region
Proceeds in simultaneous cephalic and caudal directions
What are the ends of the neural tube called and when do they close?
Anterior neuropore (day 25) Posterior neuropore (day 27)
Briefly outline spinal cord differentiation
Neuroectoderm/epithelial cells → neuroblasts → form inner mantle layer of spinal cord (grey matter) → outer marginal layer containing fibres from mantle (white matter)
What do the neuroepithelial cells lining the neural tube differentiate into, under the influence of Notch and Delta signalling?
Neuroblasts or glioblasts
In development, in which zone are glial cells found?
Ventricular zone
In development, in which zone are neuroblasts found?
Mantle zone
In development, in which zone are axons found?
Marginal zone
In which week of development does the neural tube begin to differentiate into dorsal and ventral aspects?
Week 5
What are the dorsal aspects
of the neural tube called and what does it become?
Alar plates
Sensory/dorsal horn
What are the ventral aspects of the neural tube called and what does it become?
Basal plates
Motor/ventral horn
In spinal cord development, what is the sulcus limitans?
Longitudinal groove separating the basal and alar plates
In spinal cord development, what are the roof and floor plates and what is their function?
Dorsal (roof) and ventral (floor) midline portions of spinal cord which do not contain neuroblasts; pathways for nerve fibres to cross from one side of the spinal cord to the other
In what week are the dorsal and ventral horns formed?
Week 7-8
What neurons are present in the intermediate horn of the spinal cord and where is this found?
Sympathetic neurons of the autonomic system
Thoracic and upper lumbar segments only
What separates the 2 alar plates from each other?
Dorsal median septum
What separates the 2 basal plates from each other?
Ventral fissure
What is the major difference between development of dorsal and ventral spinal nerves?
Ventral/motor nerves arise from the ventral horn and grow outwards; dorsal/sensory nerves arise from dorsal root ganglia and grow inwards to the dorsal horn
What cells are produced from differentiation of glioblasts?
Protoplasmic/fibrillar astrocytes - support/metabolism
Oligodendroglia - myelin sheath formation
Microglia - phagocytic
In what week of gestation does brain development occur?
Week 3
How many primary brain vesicles are formed from the neural tube and what are they called?
3
Forebrain - prosencephalon
Midbrain - mesencephalon
Hindbrain - rhombencephalon
What folds/flexures are present in the early brain due to uneven growth?
Midbrain cephalic flexure
Pontine flexure
Cervical flexure
What does the forebrain/prosencephalon give rise to?
Telencephalon
Diencephalon
What does the telencephalon give rise to?
Cerebrum (right and left cerebral hemispheres)
What does the diencephalon give rise to?
Eye cup
Thalamus
Hypothalamus
Epithalamus
What is the epithalamus?
A part of the dorsal forebrain including the pineal gland and a region in the roof of the third ventricle
What does the midbrain/mesencephalon give rise to?
Does not divide
What does the hindbrain/rhombencephalon give rise to?
Metencephalon
Myelencephalon
What does the metencephalon give rise to?
Pons
Cerebellum
What does the myelencephalon give rise to?
Medulla oblongata
In what week of gestation do the secondary brain vesicles develop?
Week 5
Until which level does the sulcus limitans extend?
Midbrain
What condition is caused by failed/incomplete closure of the anterior neuropore?
Anencephaly
What condition is caused by failed/incomplete closure of the posterior neuropore?
Spina bifida
In what region is spina bifida most common?
Lumbosacral
What can be given in the early stages of pregnancy to reduce risk of neural tube defects?
Folic acid
Name 2 neural tube defects
Anencephaly
Spina bifida
What are the 3 types of spina bifida?
Occulta - incomplete vertebrae but no spinal cord protrusion
Meningocele - normal vertebrae but meninges protrude
Myelomeningocele - protruding mass of nervous tissue
What is hydrocephalus?
Condition associated with spina bifida; cerebral anomaly resulting in raised pressure and large head
What is a chiari malformation?
Abnormality which causes the cerebellum to be pushed down into the spinal canal (obstruction of foramen magnum)
What is spina bifida cystica?
Encompasses meningocele and myelomeningocele types
What is a syringomyelia?
CSF filled cyst within the spinal cord
How is a chiari malformation treated?
Decompression - removal of sections of bone from the skull to allow more room
From what cells do the meninges develop?
Mesenchymal and neural crest cells
In meninges development, what happens at days 20-35 of gestation?
Mesenchymal and neural crest cells migrate around the neural tube to form an external (dura) and internal (pia and arachnoid) layer
What meningeal layers arise exclusively from neural crest cells?
Pia and arachnoid mater
What is the ependyma?
The thin membrane of glial cells lining the ventricles of the brain and the central canal of the spinal cord
How is the choroid plexus formed?
Fusion of pia mater with ependyma
From which germ layer do the meninges form?
Mesoderm
Where do meninges in the trunk/caudal region arise from?
Paraxial mesoderm
At what time points do the dura, arachnoid and pia mater layers develop?
Pia - day 24
Dura - day 45
Arachnoid - day 57
How much CSF is produced daily?
400-500ml
How much CSF is circulating at any one time?
125-150ml
What is the importance of the buoyancy CSF provides for the brain?
Ensures the weight of the brain does not compress the cranial nerves on the inside of the skull
What is the choroid plexus?
Sac-like invaginations projecting into the ventricular cavity in the roof of the 4th ventricle which produce CSF
Where does CSF circulate?
Subarachnoid space
What effect does obstruction of the foramen magnum have on CSF circulation?
CSF builds up in the head and cannot drain out which increases intracranial pressure, compressing the brain
How can increased ICP due to CSF build up be treated?
Inserting a shunt to drain the fluid
Which structures are most likely to fail to develop in ancencephaly?
Telencephalon
Brain, skull, scalp
What type of cell makes up the lens of the eye?
Epithelial
What are lens fibres?
Long, thin, transparent cells which lie under the epithelial cells of the lens
What type of protein is abundant in the lens of the eye?
Crystallins
When in gestation does eye development occur?
Weeks 3-10
When and how do the eyes first appear?
Pair of shallow grooves at day 22
What are the optic vesicles?
Outgrowths of the diencephalon which are in contact with surface ectoderm and induce changes necessary for lens formation (lens placode)
What happens to the cells in the lens placode?
Become columnar and invaginate to form a double walled cup structure
Briefly describe how the blood supply to the eye develops
Grooves arise on ventral surface of the optic cup (choroidal fissure) → a branch of the ophthalmic artery (hyaloid artery) passes along the fissure to supply the lens and retina
Describe the structure of the optic cup
Bilaminar - outer layer forms pigmented layer of the retina’ inner/neural layer forms rods, cones and neuronal cell bodies
What structures arise from the rim of the optic cup?
Iris and ciliary body
How are the cells of the lens arranged?
Laminar pattern for transparency
Briefly outline the development of the optic nerve
Optic cup connected to brain by optic stalk → inner layer cells provide network of neuroglia to support optic nerve fibres → inner and outer layers fuse and stalk cavity disappears → optic stalk becomes the optic nerve
What do the hyaloid artery and vein become?
Central artery and vein of the retina
Briefly outline the development of the eyeball
Mesenchyme around optic cup condenses to form choroid and sclera → anterior cornea becomes transparent → space develops between cornea and lens (anterior chamber) → fibrous tissue and gelatinous substance fills the space between lens and retina (posterior chamber)
Briefly outline the development of the eyelids
Folds of ectoderm grow over the cornea and fuse to form a conjunctival sac in front of the cornea → inner layer of ectoderm becomes the conjunctiva and fuses with the cornea → lacrimal glands form as ectodermal buds from the upper conjunctival sac → eyelids separate
When do the eyelids separate in gestation?
Between months 5-7
What is the role of SHH in development of the eye?
Responsible for eye field separation - upregulates PAX2 in optic stalks and restricts PAX6 to optic cup and lens
What developmental disorders can occur in the eyes?
Congenital cataracts (genetic/rubella)
Microphthalmia (FAS/infection/genetic)
Anophthalmia (genetic/infection)
Cyclopia (SHH mutation)
In which facial bone is the infra-orbital foramen located?
Maxilla
What bones make up the norma frontalis?
Frontal bone, zygomatic bone, maxillae, nasal bones, mandible
Which cranial nerve supplies the sublingual, submandibular and lacrimal glands?
Facial nerve (CN 7)
Which cranial nerve supplies the parotid gland?
Glossopharyngeal nerve (CN 9)
What is the function of the buccinator muscle and which cranial nerve is it supplied by?
Compresses the oral vestibule during chewing
Buccal branch of the facial nerve
What is the embryological origin of the buccinator muscle?
Derived from the 2nd branchial arch in development
What is the oral vestible?
Area of the mouth between the cheek and teeth
Which muscles are involved in elevation of the mandible?
Masseter, temporalis and pterygoid (lateral and medial) muscles
What problem might a patient with unilateral facial palsy have with their eye?
Inability to close the eye, causing corneal scarring
How is the integrity of the facial nerve tested?
Ask the patient to make various facial expressions
What is the mechanism of shingles infection?
Chickenpox virus can lie dormant in the sensory ganglion and reactivate as shingles later in life affecting only a specific dermatome
What regions of the face drain to the parotid lymph nodes?
Forehead
Skull
External ear
What are relaxed skin tension lines and what is their clinical significance?
Natural lines in the skin which are aligned with the collagen of the dermis – incisions along the lines are more likely to heal better without scarring
What is the area above the upper lip called?
Philtrum
Why are small, closely placed sutures favoured in treating facial wounds?
For cosmetic reasons and to avoid gaping which occurs commonly in this area because the muscles are close to the surface of the skin
What CNS drugs are fast-acting?
Anaesthetics
Cocaine
What CNS drugs are slow-acting?
Antidepressants
Antipsychotics
Why is drug entry to the CNS restricted and how has this been overcome?
BBB
Pro-drugs (e.g. L-DOPA), carrier molecules, transient disruption of barrier (e.g. mannitol)
What is an agonist?
Activates a receptor, producing a functional response in the cell
What is an antagonist?
Binds to the receptor without activating it, blocking the action of agonists
What is a partial agonist?
Partially activates a receptor, producing a functional response in the cell
What are general anaesthetics, how are they administered, how do they work and give some examples
Drugs used to produce surgical anaesthesia
Inhalational or intravenous
Act on ion channels (e.g GABA receptor)
Halothane (IH), propofol (IV)
What are anxiolytics, how do they work and give some examples
Drugs which cause sleep and reduce anxiety
Potentiate action of GABA Barbituates (e.g. pentobarbitone), benzodiazepines (e.g. diazepam)
What are antipsychotics and give some examples
Drugs which are effective in relieving the symptoms of schizophrenic illness
Typical (chlorpromazine, haloperidol), atypical (clozapine, olanzapine)
What are antidepressants, how along do they take to work and give some examples
Drugs which alleviate symptoms of depressive illness
2-4 weeks
MOIs (phenelzine), tricyclic antidepressants (imipramine), SSRIs (fluoxetine), ketamine (rapid onset)
What are analgesics and give some examples
Drugs used clinically for controlling pain
Opiates (morphine, buprenorphine), NSAIDs (ibuprofen, aspirin)
What are psychomimetics/hallucinogens and give some examples
Drugs which cause disturbance of perception and behaviour which cannot be simply characterised by sedative/stimulant effects
LSD, mescaline, ketamine, phencyclidine, THC (cannabis)
What are cognition enhancers/nootropic drugs and give some examples
Drugs which improve memory and cognitive performance
Galantamine, donepezil
What is a common drug for epilepsy?
Gabapentin
What is a common drug for Parkinson’s?
L-DOPA
What is a common drug for bipolar disease?
Lithium
What diseases/processes are regulated by dopaminergic transmission?
Parkinson’s, schizophrenia, hormone regulation, addiction and vomiting control
What areas of the brain produce dopamine?
Substantia nigra, ventral tegmental area, hypothalamus
What are the main dopamine pathways, what do they do and what disorder is associated with them?
Nigrostriatal → behavioural effects → Parkinson’s disease
Tuberohypophyseal → prolactin secretion → galactorrhoea
Medulla → vomit response → vomiting
In what part of the substantia nigra are dopamine producing cells located?
Pars compacta
What are the main signs of Parkinson’s disease?
Resting tremor, hypokinesia, cogwheel/lead pipe rigidity
What is often the first sign of Parkinson’s disease?
Loss of sense of smell
What risk factors are associated with Parkinson’s disease?
Ageing, genetic factors (synuclein, parkin), environmental factors (toxins, herbicides, pesticides)
What protein is associated with Parkinson’s disease?
Synuclein; deposited in protein aggregates in dying dopamine cells (Lewy bodies)
What are the 3 ways in which dopaminergic signalling can be enhanced therapeutically?
Replace dopamine (e.g. L-DOPA) Mimic actions of dopamine (D2/3 agonists e.g. bromocriptine) Reduce breakdown of dopamine (MOAIs e.g. selegiline)
What are the limitations of L-DOPA treatment?
Effective initially but only 20% response at 5 years
On/off episodes
What are the side-effects of D2/3 agonists?
Hallucinations
Pathological gambling/shopping
What are the symptoms of schizophrenia?
Positive – hallucinations (hearing voices), delusions (persecution or grandeur), disorder of logical thought
Negative - sustained depression, anhedonia (inability to feel pleasure), avolition (lack of drive), slow thought/speech/actions, lack of recognition of illness
Cognitive - difficulties in learning, planning and paying attention
What is the mechanism of action of schizophrenia drugs such as haloperidol and clozapine?
Reduce dopaminergic signalling at D2 dopamine receptors (D2 antagonists)
What are the limitations of D2 antagonists for schizophrenia treatment?
D2 receptor blockade is immediate, but therapeutic benefit takes weeks to appear
Some patients do not respond, despite D2 receptor blockade
These drugs are effective against the positive symptoms, but not against the negative and cognitive symptoms
What are the side-effects of D2 antagonists?
Parkinson’s disease-like symptoms, prolactin hypersecretion, postural hypotension, sedation, dry mouth, weight gain
How is dopamine released in the hypothalamus and what is its action?
Dopamine cell bodies in arcuate nucleus of the hypothalamus have terminals in median eminence – secrete dopamine into the portal blood vessels leading to the anterior pituitary
Dopamine binds to D2 dopamine receptors on prolactin-secretin cells to inhibit prolactin secretion
