PBL Topic 3 Case 2 Flashcards
What do mechanoreceptors detect?
- Mechanical compression or stretching of tissue adjacent to the receptor
What do thermoreceptors detect?
- Changes in temperature, some cold, others warmth
What do nociceptors detect?
- Damage occurring in tissue e.g. physical or chemical damage
What do electromagnetic receptors detect?
- Light on the retina of the eye
What do chemoreceptors detect?
- Taste in the mouth
- Smell in the nose
- Oxygen level in the blood
- Osmolality of blood
- [CO2]
What is a modality of sensation?
- Any principal type of sensation a person experiecnes
What is the labelled line principle?
- Specific nerve fibres transmit only one modality of sensation
- Since they terminate at a specific site in the CNS
What is a receptor potential?
- Change in membrane electrical potential whenever the receptor is stimulated
How does a stimulus cause an action potential?
- Stimulus excites a receptor
- Change in membrane permeability allowing diffusion of ions through the membrane
- Receptor potential rises above a threshold to generate an action potential
What is meant by receptor adaptation?
- The rate at which a receptor responds to a stimulus until the rate of action potential ceases
What is a tonic receptor? Give an example of a tonic receptor
- Slowly adapting
- Transmits continuous impulses to the brain as long as the stimulus is present
- Muscle spindle or Golgi tendon
What is a rate receptor? Give an example of a rate receptor
- Rapidly adapting
- Transmits signals only when the stimulus changes strength
- Pacinian corpuscle
How does a type A fibre compare to a type C fibre?
- Type A are larger and myelinated, transmission is faster
- Type C are smaller and unmyelinated, transmission is slower
Give two examples A-alpha fibre
- Annulospiral ending of muscle spindles
- Golgi tendon organs
Give an example of an A-beta fibre
- Cutaneous tactile receptor
Give an example of an A-gamma fibre
- Flower spray ending of muscle spindles
Give an example of an A-delta fibre
- Nociceptor carrying temperature, crude touch and pricking sensation
Give an example of a C fibre
- Pain and crude touch sensation
What is spatial summation?
- Signal strength increases by using progressively greater number of fibres
What is temporal summation?
- Signal strength increases by increasing number of impulses from each fibre
Outline the structure of a free nerve ending
- Nerve loses its Schwann cell sheath as it reaches dermis or epidermis
Identify two modalities that free nerve endings detect
- Temperature
- Pain
Identify a modality that Merkel cells detect? How do Merkel cells adapt?
- Pressure
- Slowly
Identify three encapsulated nerve endings
- Meissner’s corpuscles
- Ruffini endings
- Pacinian corpuscles
Where are Meissner’s corpuscles most abundant?
- Finger pads
How do Meissner’s corpuscles adapt?
- Rapidly
What is the role of Meissner’s corpuscles
- Detective work on textured surfaces
Where are Ruffini endings located?
- Hairy and glabrous skin
What do Ruffini endings detect? How do they adapt?
- Drag (shearing stress) over skin
- Slowly adapting
Where are Pacinian corpuscles located?
- Side of fingers and palm
What do Pacinian corpuscles detect?
- Vibration
Where are dorsal root ganglia located?
- Intervertebral foramina
- Where they come together to form spinal nerves
What are satellite cells?
- Modified Schwann cell in spinal ganglion
What does the medial stream of the dorsal root entry zone consist of? Where do they divide and synapse?
- Medium and large fibres
- Divide into ascending and descending fibres in the posterior funiculus
- Which synapse in laminae 2, 4 and 4
What does the lateral stream of the dorsal root entry zone consist of? Where do they divide and synapse?
- Small fibres
- Divide into ascending and descending fibres in the posterolateral tract of Lissauer
- Which synapse in the laminae 1 (marginal zone) and the substantia gelatinosa (lamina 2)
Identify the two major somatic sensory pathways
- Dorsal column medial lemniscal system
- Spinothalamic pathway
Where are the first-order neurons of the somatic sensory pathways located?
- Posterior root ganglia
Where are the second-order neurons of the somatic sensory pathways located?
- CNS grey matter on same side as first order neurons
Where are the third-order neurons of the somatic sensory pathways located
- Between thalamus and somatosensory cortex
Outline 3 differences between the DCML and spinothalamic systems
- DCML consists of large fibres which transmit at high velocities
- DCML has a high degree of spatial orientation of fibres
- Spinothalamic transmits a broad spectrum of sensory modalities
Identify 4 modalities transmitted in the DCML
- Touch sensation
- Vibration sensation
- Proprioception
- Pressure
Identify 2 modalities transmitted in the anterior spinothalamic tract
- Crude touch
- Firm pressure sensations
Identify 2 modalities transmitted in the lateral spinothalamic tract
- Pain
- Temperature
Identify six sensory receptors that transmit impulses in the DCML
- Meissner’s corpuscles
- Pacinian corpuscles
- Ruffini endings
- Merkel cells
- Muscle spindles
- Golgi tendon organs
What are the fasciculus gracilis and nucleus gracilis?
- First order neurons from lower limbs ascend in fasciculus gracilis
- And terminate in nucleus gracilis in medulla oblongata
What are the fasciculus cuneatus and nucleus cuneatus?
- First order neurons from upper limbs and torso ascend in fasciculus cuneatus
- And terminate in nucleus cuneatus in medulla oblongata
Where do second order neurons of the DCML project from and to?
- From nucleus gracilis and nucleus cuneatus
- To ventral posterolateral nucleus of thalamus
What terminates in the ventral posteromedial nucleus?
- Fibres from trigeminal lemniscus
- Which subserve same sensory functions for the head that the DCML fibres subserve for the body
Where do third order neurons of the DCML project from and to?
- From VPN
- To somatosensory cortex in postcentral gyrus
Where do second order neurons of the spinothalamic project from and to?
- From lamina 1-2 and 4-5
- To contralateral VPN
Identify the pathway of the spinothalamic system
- Second order neurons enter lamina 1-2, 4-5
- Decussate immediately
- Pass in anterior and lateral funiculus
- Come together at spinal lemniscus
- Synapse in contralateral VPN
Where does the spinoreticular tract run and terminate?
- Runs alongside spinothalamic pathway
- Reticular activating system
Identify two functions of the spinoreticular tracts
- Report to limbic cortex of anterior cingulate gyrus about the nature of a sensation e.g. pleasurable or painful
- Arouse cerebral cortex e.g. waking state
Where does the spinotectal tract run and terminate?
- Runs alongside spinothalamic pathway
- Terminates in superior colliculus
Identify a function of the spinotectal tract?
- Mediates reflex postural movements of head in response to visual stimuli
Where does spino-olivary tract terminate and what is its role?
- Inferior olivary nucleus in medulla
- Motor learning through its action on contralateral cerebellar cortex
Identify the three nuclei of the trigeminal sensory nuclei and their roles?
- Mesencephalic: proprioception
- Chief: Touch and pressure
- Spinal: Pain
Identify three other cranial nerves that convey sensory information to the trigeminal sensory nucleus
- Facial
- Glossopharyngeal
- Vagus
Where does the trigeminothalamic tract run from and to?
- Spinal trigeminal lemniscus
- Terminates in ventral posteromedial nucleus of the thalamus
- Third order afferents to somatosensory cortex
Describe the layout of the homunculus of the somatosensory cortex
- Tongue and larynx closest to horizontal fissure
- Large representation of lips and thumb
- Lower limb and foot closest to longitudinal fissure
Which of Broadmann’s areas does the somatosensory cortex reside in?
- 3, 1 and 2
Area 3a of the somatosensory cortex receives information from which receptors?
- Muscle spindles
Area 3b of the somatosensory cortex receives information from which receptors?
- Cutaneous receptors
Identify three afferents to the somatosensory cortex
- Thalamic afferents
- Commissural fibres from opposite somatosensory cortex
- Association fibres form motor cortex
What is stereoanesthesia and what is a common cause?
- Reduction of sensory acuity on opposite side of body
- Including raised sensory threshold, poor two-point discrimination, and impaired vibration sense and position sense
- Middle meningeal artery is compromised
Identify three efferents to the somatosensory cortex
- Association fibres to ipsilateral motor cortex
- Commissural fibres to contralateral somatosensory cortex
- Projection fibres to pyramidal tract to terminate on inhibitory internuncial neurons
Where are somatosensory association areas located and what is their role?
- Broadmann’s areas 5 and 7
- Deciphering deeper meanings of inputs to somatosensory cortex
What is pain?
- Unpleasant emotional experience associated with tissue damage
What is allodynia?
- Pain produced by an innocuous stimuli
- For example stroking sunburned skin or moving an inflamed joint
What are central pain-projecting neurons?
- Posterior horn neurons projecting pain-encoded information to the contralateral brainstem and thalamic nuclei
- Includes spinothalamic, spinoreticular and spinoamygdaloid pathways
What is wind-up phenomenon?
- Sustained state of excitation of central pain pathways induced by glutamate activation of NMDA receptors
What is fast pain?
- Stabbing pain perceived by activation of A-delta nociceptors
What is hyperalgesia?
- Hypersensitivity to stimulation of injured tissue and of surrounding tissue
What is neurogenic inflammation?
- Inflammation caused by liberation of substance P
- Following depolarisation of antidromic fine peripheral nerve fibres
What is neuropathic pain?
- Chronic stabbing or burning pain associated to peripheral nerve
What are nociceptors?
- Receptors whose activation generates a sense of pain
What are polymodal receptors?
- Peripheral nociceptors responsive to noxious stimulation
What is sensitisation?
- Lowering of threshold of peripheral nociceptors by histamine
- Following peripheral release of peptides via the axon reflex
What is slow pain?
- Aching pain perceived following activation of C-fibre nociceptors
Identify three molecules that lower the activation threshold of nociceptors following tissue injury
- Bradykinin
- Prostaglandin
- Leukotrienes
What does substance P bind to? How does this result in production of arachidonic acid?
- Substance P binds to mast cells
- Mast cells secrete histamine
- Which binds to histamine receptors on nerve terminals
- Causing production of arachidonic acid
What happens to the arachidonic acid during tissue damage?
- Cyclooxidase converts arachidonic acid into prostaglandin
- Which results in sustained activation of large numbers of C-fibres and sensitisation of nociceptors
- Manifested by allodynia and hyperalgesia
What is the lateral pain pathway?
- Projecting of pain via the lateral spinothalamic tract to the contralateral ventral posterolateral nucleus to the primary motor cortex
- This pathway activates spinotectal tract which causes eye to look towards source of pain
What is the medial pain pathway?
- Projecting of pain via the spinoreticular tracts to anterior cingulate cortex via intralaminar nucleus of thalamus
- This area is concerned with the affective component of pain
Identify three causes of central pain states
- Repetitive activation of NMDA glutamate receptors
- Gene transcription involving addition of glutamate receptors
- Non-serotonergic neurons near the magnus raphe nucleus facilitate central pain states
Identify the pathology of neuropathic pain
- Peripheral nerve is severed
- Proximal and distal end become separated by developing scar tissue
- Intermediate regenerating axon from a thread like ball known as a neuroma
Identify one cause of neuropathic pain
- Postherpetic neuralgia (shingles)
Outline the axon reflex
- Skin is stroked by a sharp object
- Red flare owing to arteriolar dilatation
- White wheal owing to exudation of plasma
- Due to release of Substance P which binds to surface of mast cells which release histamine
What is segmental antinociception?
- Large type A mechanoreceptive afferents from hair follicles synapse upon anterior spinothalamic relay cells
- They (mainly GABA) gelatinosa cells which synapse in turn upon lateral spinothalamic relay cells.
- Some of the internuncials also exert presynaptic inhibition upon C-fibre terminals.
- Gating of the spinothalamic response to C-fibre activity can be induced by stimulating the mechanoreceptive afferents, thereby recruiting inhibitory gelatinosa cells.
What is supraspinal antinociception?
- Raphespinal tract descends from magnus raphe nucleus
- Which descends in Lissauer’s tract to terminate in substantia gelatinosa
- Liberation of serotonin excites inhibitory internuncials causing synaptic inhibition.
Stimulation of which brain region results in stimulation of the magnus raphe nucleus?
- Periaqueductal grey of the midbrain
What is the role of beta-endorphin in analgesia?
- Released from hypothalamic neurons which project to PAG during stress
- These neurons inhibitory internuncials on the PAG
- Resulting in increased stimulation of the MRN and hence antinociception
What is cervical spondylosis?
- Osteoarthritis in the cervical spine
- Characterised by degeneration of the intervertebral disc and osteophyte formation
What is cervical spondylotic radiculopathy?
- Compression of a nerve root when a disc prolapses laterally
Outline the clinical features of cervical spondylotic radiculopathy.
- Pain in the neck and affected segment
- Neck held rigidly and movements may exacerbate pain
- Paraesthesia and sensory loss in the affected segment
- Weakness, wasting, reflex impairment
Outline the muscle weakness, sensory loss and reflex loss associated with a C5 root compression
- Biceps, deltoid
- Upper lateral arm
- Biceps reflex
Outline the muscle weakness, sensory loss and reflex loss associated with a C6 root compression
- Brachioradialis
- Lower lateral arm, thumb, index finger
- Supinator
Outline the muscle weakness, sensory loss and reflex loss associated with a C7 root compression
- Triceps, fingers and wrist extensors
- Middle finger
- Triceps
Outline the treatment options for cervical spondylotic radiculopathy.
- Analgesics and physiotherapy
- Disc excision (MRI required)
What is cervical spondylotic myelopathy?
- Pressure on the spinal cord in the cervical region due to herniation of a disc
Outline the clinical features of cervical spondylotic myelopathy.
- Spasticity of legs comes first
- Sensory loss in upper limbs, tingling, numbness, proprioception loss in hands, with progressive numbness
Outline the treatment options for cervical spondylotic myelopathy.
- Anterior discectomy
- Which may arrest progression but may not result in neurological improvement
What is lumbar spondylosis?
- Degenerative disc disease and osteoarthritic changes in the lumbar spine
- Sciatica
Outline the pathology of lumbar disc herniation
- Precipitated by trauma
- Nucleus pulposus may budge or rupture through annulus fibrosus
- Giving rise to pressure on nerve endings in spinal ligaments
Outline the clinical features of lumbar disc herniation
- Lasegues sign: limitation of flexion of the hip on the affected side if the straight leg is raised
- Acute onset lower back pain and sciatica
- Reflex loss
- Sensory loss in affected dermatome
Outline the muscle weakness, sensory loss and reflex loss associated with a L4 root compression
- Inversion of foot
- Inner calf
- Knee
Outline the muscle weakness, sensory loss associated with a L5 root compression
- Dorsiflexion of great toe
- Outer calf and dorsum of foot
Outline the muscle weakness, sensory loss and reflex loss associated with a S1 root compression
- Plantar flexion
- Sole and lateral foot
- Ankle
Identify 4 things that X-rays of the skull and spine show
- Fracture
- Vault and skull disease
- Enlargement or destruction of pituitary fossa
- Intracranial calcification
What is an opioid?
- A substance that produces morphine like effects
- That is blocked by naloxone, a complete antagonist
Identify the opioid receptor responsible for most of the analgesic effects.
- u receptor
Describe how opioids decrease neuronal excitability
- Opening inward-rectifying potassium channels, causing hyperpolarisation
- Inhibiting the opening of N-type calcium channels, resulting in reduced neurotransmitter release
How are opioids inactivated?
- Hepatic metabolism
- In conjunction with glucuronide
Outline five adverse effects of opioids
- Tolerance
- Dependence
- Euphoria
- Sedation
- Respiratory depression
Outline the roles of COX-1 and COX-2
- COX-1 is involved in tissue homeostasis and prostaglandin production
- COX-2 is involved in production of prostanoid mediators of inflammation
Describe the mechanism behind the anti-inflammatory effect of NSAIDs
- Decrease in prostaglandin E2 and prostacyclin
- Which reduces vasodilation and oedema
Describe the mechanism behind the anti-analgesic effects of NSAIDs
- Decrease prostaglandins generation
- So less sensitisation of nociceptive nerve endings to inflammatory mediators such as bradykinin and 5-HT
Describe the mechanism behind the anti-pyretic effect of NSAIDs
- Inhibit IL-1 beta release
Identify two examples of NSAIDs
- Ibuprofen
- Naproxen
What is the dosage of ibuprofen?
- 300-400 mg
- 3 - 4 times a day
Outline two unwanted effects of NSAIDs
- GI disturbances (gastric ulceration / bleeding)
- Skin reactions
Explain the rationale behind co-administration of NSAIDs and opioids
- Same degree of analgesia
- But reduced addiction
Explain the actions of paracetamol
- Antipyretic
- Analgesic
- But less anti-inflammatory effects
Identify two drugs that can prevent liver damage and how they work
- I. V Acetylcysteine
- Oral methionine
- Increase glutathione
What is the dosage of paracetamol?
- 0.5-1g
- Every 4-6 hours
What is neuropathic pain and when does it occur?
- Dysfunction of pain perception apparatus
- Caused by trigeminal neuralgia / diabetic neuropathy
- Opioid resistant
Explain how TCAs can be used to treat neuropathic pain
- Inhibit noradrenaline re-uptake
Explain how gabapentin can be used to treat neuropathic pain
- Bind to alpha 2 delta 1 and alpha 2 delta 2 subunits of potassium channels
- And inhibit neurotransmitter release
What is the dosage of gabapentin?
- 300 mg once daily on day 1
- 300 mg twice daily on day 2
- 300 mg three times daily on day 3
Explain how lidocaine can be used to treat neuropathic pain
- Blocks spontaneous discharges from damaged sensory nerve terminals
How is lidocaine administered?
- Topically as a patch
- Or intravenously
Outline the WHO Analgesic Pain Ladder
- Step 1: Paracetamol
- Step 2: If pain persists or increases (moderate pain), weak opioid such as codeine
- Step 3: Severe pain, give a strong opioid such as morphine
What is drug dependence?
- Condition in which drug taking becomes compulsive, often with serious adverse consequences
Explain why psychoactive drugs produce a rewarding experience e.g. elevation in mood or feeling of euphoria
- Activate mesolimbic dopaminergic pathway running from the VTA to the nucleus accumbens
- They enhance firing of VTA dopaminergic neurons
- By reducing the level of GABAergic inhibition within the VTA
Explain how drugs alter memory formation to enhance the recollection of previous drug experiences
- Changes in synaptic plasticity by enhancing long-term potentiation
- By increasing expression of AMPA receptors
What is withdrawal syndrome?
- Cessation of drug administration / administration of an antagonist producing adverse effects characteristic of the drug taken
Outline the mechanisms responsible for the withdrawal syndrome
- Increase in cAMP production as a result of super activation of adenylyl cyclase
- Activation of protein kinases
- Resulting in excitation of nerve terminals by phosphorylation neurotransmitter transporters
- Thus increasing conductance and increasing neurotransmitter release
What is tolerance?
- Decrease in pharmacological effects on repeated administration of a drug
Outline the mechanisms responsible for tolerance
- u receptor is phosphorylated by various intracellular kinases
- That desensitise the receptor or cause the receptor to be blocked by other binding proteins
Outline the process of plain radiography
- X rays are collimated (directed) to appropriate area
- The X-rays are attenuated by the tissue
- Air attenuates X-rays a little
- Fat attenuates X-rays more than air but less than water
- Bone attenuates X-rays the most
- Differences in attenuation result in differences in level of exposure on the film
Why does bone appear white on plain radiography?
- Most attenuation of X-rays
- Meaning it is exposed to least amount of X-rays
Why does air appear black on plain radiography?
- Least attenuation of X-rays
- Meaning it is exposed to most amount of X-rays
Identify a substance used to fill structures to increase attenuation of X-rays
- Barium sulfate
Identify a contrast agent injected directly into veins or arteries during plain radiography
- Iodine based molecules
What does Computed Tomography involve?
- X-ray tube passes around the body
- Creating a series of images
- Which are transformed using a computer to produce final image
Identify 5 limitations of CT
- Lesions under 1 cm in diameter may be missed,
- Lesions with attenuation close to bone may be missed if near the skull,
- Lesions with attenuation similar to brain are poorly displayed e.g. MS plaques, isodense subdural haematoma.
- CT is not good at detecting posterior fossa lesions because of surrounding bone,
- Patient co-operation: an anaesthetic is very occasionally needed.
Outline the process of magnetic resonance imaging
- Protons in water molecules of patient act as magnet
- Patient is placed in strong magnetic field which aligns the protons
- Radio waves are passed through the body and cause the magnets to deflect
- As they return to their aligned position they emit small radio pulses
- The strength and frequency of pulses produces a signal which is analysed by a powerful computer
What are T1 and T2 images and how are they produced?
- Sequence of radio waves is altered to produce either T1 or T2 images
- T1 images show dark fluid
- T2 images show bright fluid
What i.v contrast is used during MRI when assessing cerebral circulation?
- Gadolinium
Identify five advantages of MRI
- Distinguishes between white and grey matter in the spinal cord,
- MRI has resolution superior to CT (around 0.5 cm),
- No radiation is involved
- Capable of pituitary imaging
- Tumours, infarction, haemorrhage, MS plaques, posterior fossa, foramen magnum and cord are demonstrated well by MRI.
Identify four disadvantages of MRI
- Time
- Cost
- Patients need to keep still within a narrow tube and thus claustrophobia is an issue
- Patients with pacemakers or metallic fragments in the brain cannot be imaged
- MR imaging frequently shows diffuse meningeal enhancement with gadolinium for some days after lumbar puncture.
Outline the process of PET scanning
- Positrons are positively charged ‘anti-electrons’.
- Which are emitted from the decay of proton-rich radionuclides.
- The most commonly used radionuclide is fluorodeoxyglucose (FDG)
- Tissues actively metabolising glucose take up FDG, the resulting localised high concentration of this molecule compared to background emission is detected as a “hot spot.”
Define Gate Control Theory
- A gate exists that, when opened sends information to an action system which results in perception of pain
- Pain is not only understood in terms of stimulus response pathways
- But is also affected by emotional and behavioural factors
According to Gate Control Theory, identify physical factors that open and close the gate.
- Open: Injury or activation of large nociceptive fibres
- Closure: Medication, stimulation of small fibres
According to Gate Control Theory, identify emotional factors that open and close the gate.
- Open: Anxiety, worry, tension, depression
- Closure: Happiness, optimism, relaxation
According to Gate Control Theory, identify behavioural factors that open and close the gate.
- Open: Focussing on pain
- Closure: Concentration, distraction or involvement of other activities
Explain how learning plays a role in the processing of pain
- Classical conditioning: associating an environmental stimulus with pain
- Operant conditioning: positive reinforcement includes sympathy, time off work
What are fear avoidance beliefs?
- Pain related fear results in hyper-vigilance towards the pain
- Which would contribute to the progression from acute to chronic pain
Identify the three components of catastrophising
- Rumination: a focus on threatening information e.g. a symptom
- Magnification: overestimating the extent of the threat e.g. the severity of the symptom
- Helplessness: underestimating personal and broader resources that might help mitigate the danger e.g. visiting doctor / treatments
How does treatment of chronic pain differ to that of acute pain?
- Acute pain = pharmacological interventions
- Chronic pain = multidisciplinary approach to pain with focus on:
- Improving functioning
- Decreasing reliance on medical services
- Increasing social support
Outline three methods of pain relief that reflect an interaction between psychology and physiological factors
- Respondent methods: Reducing muscular tension and anxiety to reduce pain
- Cognitive methods: modifying thoughts about pain that may exacerbate pain
- Behavioural methods - Which draw upon operant conditioning and reinforcement
Outline Black Report
- Cultural explanation: health influenced by culture
- Materialist explanation: health influenced by economic factors
- Social selection hypothesis: health influences social class not the other way around
- Artefact explanation: No significant relationship between health and class
What is drift hypothesis?
- Mental illness causes a downward shift in social class
What is social causation theory?
- Low social status causes stress that leads to mental illness
