Week 19-20 - Peripheral Neuropathy & Spinal Cord Injury Flashcards
Epineurium
Surrounds entire nerve
Perineurium
Encapsulates fascicle of nerves (bundles of axons)
Endoneurium
Contained within the perineurium and coating axons.
Blood-nerve barrier
between inner perineurium and endothelial cells of microvasculature within endoneurium
What are special senses?
Modalities that are carried by cranial nerves (i.e., olfaction, vision, tase, hearing/balance)
What are somatic senses?
Detected from all parts of the body (and head) and transmitted to the CNS via all spinal nerves except for C1 and the trigeminal nerve. Distinct from special senses, which are only carried by cranial nerves (i.e., vision, taste)>
Types of sensory receptors (4)
photoreceptors (rods and cones) thermoreceptors (central and peripheral) Nociceptors Mechanoreceptors (exteroreceptors and proprioceptors)
2 types of mechanoreceptors
Exteroreceptors respond to stimuli from outside the body (i.e., touch);
Proprioreceptors give information about position of the body, or its parts.
Generator potential vs action potential
Generator Potential is graded in amplitude (bigger stimulus has bigger GP) and does not cause the membrane to be refractory, nor does it actively propagate. Action potentials are all or nothing. They do cause membrane to bcm refractory to prevent backward propagation and they are actively propagated by regenerating themselves along the axonal membrane.
what is meant by the concept that the neuromuscular junction has a high safety factor
This refers to the fact that every alpha motor neuron AP will result in a muscle AP and subsequent contraction. Many parts of the physiology have developed to make this the reality (lots of VGNaCs etc).
Definition of anemia
A decrease in blood hemoglobin concentration. Can be the result of decreased RBCs or increased plasma. Normal ranges are age and sex dependent so the diagnosis of anemia differs based on these characteristics.
best marker for iron deficiency
Ferritin. Ferritin < 30 indicative or iron deficiency.
most common cause of iron deficiency anemia in the developed world is… What are the other causes of iron deficient anemia? (3)
Most common is occult blood loss! Bleeding Diet deficiency Malabsorption Increased need (children, pregnant)
What are the causes of microcytic anemias?
Acronym: TAILS Thalassemia trait Anemia of chronic disease Iron deficiency Lead poisoning Sideroblastic anemia
How are the generator potentials produced by mechanoreceptors, nociceptors, chemoreceptors, and photoreceptors different?
Mechanoreceptors produce a generator potential DIRECTLY in response to stretch (Na/K channels open in response to stretch). In contrast, nociceptors, photoreceptors, and chemoreceptors produce generator potentials INDIRECTLY via GPCRs.
The neuromuscular junction includes…
The presynaptic terminal of the alpha motor neuron, the synaptic cleft, and the post synaptic membrane of a muscle cell.
What is a motor unit?
1 alpha motor neuron and all of the muscle fibres that it innervates.
All of the muscle fibres innervated by a motor unit are the same type of fibres (fast, slow, twitch).
What is a motor unit pool?
All of the motor units that are involved in the innervation of a skeletal muscle.
Describe the basal lamina of peripheral nerves
it surrounds both the individual axon and myelin
Explain action potential propagation along a motor neuron (4)
An AP travels along an alpha motor neuron (MN) to all of its terminal branches.
- Ca2+ influx through voltage gated Ca channels stimulates release of ACh from vesicles at the distal end of the alpha MN
- ACh binds AChRs on shoulders of post junctional folds
- Na+ and K+ flow though AChR pore, which results in muscle membrane depolarisation
- this depolarisation is the ENDPLATE POTENTIAL
- AChE in the basal lamina hydrolyzes ACh to terminate NM transmission
Where is AChE located and its role
In the basal lamina/EC matrix of the synaptic cleft. Cleans up ACh swiftly so that contraction is v discrete.
What is the point of junctional folds on the post syanptic membrane
Large SA for AChR activation (located on the shoulders of folds)
What is the perijunctional zone
It is on the periphery of the site of muscle AP initiation. Has a high density of VGNaCs to ensure that muscle membrane reaches AP threshold (EPP is almost always large enough)
What is the point of T tubules on muscle cells?
They help bring AP deep into the cell.
They are continuous with the membrane. VGCa Channels on the t tubules pair with Ryanodine receptors on the SR to induce Ca release into the muscle cell.
Myelin
Coating derived from Schwann cells in the PNS that is present on fast-conducting fibers, both motor and sensory promoting faster conduction.
Positive symptoms of peripheral neuropathy. What are they generally and the two categories.
Positive symptoms reflect inappropriate spontaneous nerve activity. May be more prominent early on. - MOTOR (cramps; twitch) - SENSORY (tingling/prickling, burning, stabbing pain, allodynia, hyperalgesia)
Allodynia
Discomfort to stimuli that are not typically painful (i.e., sensitive to bedsheets on toes)
Negative symptoms of peripheral neuropathy
Negative symptoms reflect reduced nerve activity. MOTOR - weakness; atrophy SENSORY - reduced sensation/numbness; - gait ataxia (balance is worse without visual input)
Autonomic symptoms of peripheral neuropathy (4 categories)
- Cardiac (orthostatic dizziness, labile BP, arrhythmias) - GI (early satiety, bloating, constipation, diarrhea) - Genitourinary (ED, urinary incontinence) - Vasomotor (cold extremities; skin colour changes)
Clues that it may be a demyelinating neuropathy (rather than axonal)
- weakness without atriphy - not length-dependent - early loss of reflexes - rapidly ascending sx - preceding infection
Why is it important to identify if a neuropathy is demyelinating type
Primary demyelination often involves an immune-mediated neuropathy, which are often amenable to treatment.
Causes of length-dependent, axonal polyneuropathy
Systemic metabolic disorder (i.e., diabetes, nutritional deficiencies [i.e., pernicious anemia - can’t absorb B12]); Toxins (chemo, chronic EtOH); Hereditary (Charcot-Marie-Tooth); Idiopathic (elderly);
Principles for managing peripheral neuropathy (6)
- treatunderlying cause (i.e., glycemic control) 2. Neuropathic Pain (pharma and non-pharma) 3. Bracing and orthotics 4. Multidisciplinary team (OT, PT, podiatry for foot care) 5. Education and counselling 6. Avoidance of neurotoxins
Pharmacological Management of Neuropathic Pain
- Gabapentin, TCA, SNRIs 2. tramadol, opioids 3. cannabinoids 4. 4th line agents
Non-pharma management of neuropathic pain
- CBT - address depression and anxiety - Physio - OT - Aquatherapy
What is polyradiculopathy
Pattern in which there is evidence of involvement at multiple nerve roots and additional involvement of more distal sites of the peripheral nervous system.
Charcot-Marie-Tooth What is it, what causes it, and what are the features?
The most common type of hereditary neuropathy. Encompasses a number of genetically distinct disorders. There are axonal and demyelinating subtypes. Insidious, symmetric progression. Usually painless with minimal positive symptoms. Often severe distal wekaness and sensory loss with little disability. Foot deformity (high arched feet and hammer toes). Usually positive family histories.
Guillan-Barre Syndrome
AKA Acute inflammatory demyelinating polyradiculopathy. Most common cause of acute generalized weakness. Can occur at any age. Most have had a recent infection. Sensory symptoms in periphery and trunk. Large fibre > small fibre impairment. Distal>proximal motor weakness - the predominant feature. Begins in legs and ascends to arms, trunk, head, neck. Can develop resp failure. Can have autonomic sx of hypo/hypertension and cardiac arrhythmia.
Clinical course of guillan-barre syndrom
TIMING IS SUPER IMPORTANT! progresses over 2-4 wks - plateaus - recovery over months. If they haven’t reach max abnormality at 8 wks then it isn’t GBS!
Schwaan Cells - types and functions
Can either be myelinating or demyelinating. - Produce neurotrophic & neurotopic substances - Induce receptor formation when needed - Produce extra-cellular matrix
3 levels of demyelination of peripheral nerve axons effect of each of these scenarios
- Reduction in myelin thickness - slower AP propagation 2. Complete demyelination of a segment - slower AP and Na+ channel redistribution from node of ranvier 3. Complete demyelination of several adjacent segments - AP failure because Na+ channels aren’t dense enough to support propagation. Loss of nerve cell function as long as the AP block persists.
How does remyelination work?
Damaged Schwaan cells release trophic factors and cytokines. Macrophages come and clean up remaining myelin; The same factors also trigger proliferation of undifferentiated Schwann cells, some of which differentiate into myelinating cells and wrap around the bare axon.
Tinel’s sign
Occurs when an axon has been disrupted/cut. If you tap on the proximal edge (connected to the brain), it will elicit pins and needs. Can be used clinically to monitor progression of axon regeneration.
Wallerian Degeneration
The severed chink of axon (not attached to cell body) will degenerate and won’t come back. You can’t re-connect two ends again and save it.
Peripheral nerve regeneration after injury
Cell body sends signals to upregulate factors that promote growth. Up to 10 sprouts are produced at the cut site. Each sprout has a growth cone with mobile filopodia. Interaction ebtween the growth cone and its env is key for continued elongation and direction of growth. The basal lamina from the degraded axon stump remains = the ENDONEURIAL TUBE. Schwaan cells differentiation and form pathways with the endoneurial tube to guide regrowing axon.
How quickly can nerves grow back?
~1-4 mm/day (and can be tracked by Tinel sign)
Do you get back full function after a nerve regrows?
Nope. Some sensory and motor fibres will mix up and get pruned away. Mostly sensory reinnervated sensory and vice versa so you get good recovery but not perfect.
What are nerve conduction studies for?
Nerve conduction studies are used to assess if it is a neuropraxia (AP block due to demyelination) or if the axons have been completely disrupted. The symptoms of these two are the same –> loss of fxn.
Results of nerve conduction study with neurapraxia
The axon is intact, but demyelination stops AP from continuing to the end. If the stimulator and receiver are placed on one side of the gap then it will transmit, but if they are on opposite sides of the gap then the signal won’t transmit.
Results of a nerve conduction study in the case of severed axon
Initially (before) wallerian degeneration), the study will look a lot like neurapraxia because the severed stump still exists and transmits a signal. Just like in neurapraxia, the signal won’t bypass the gap if signal and receiver are placed on either side of it. After 2-3 weeks, the stump has degraded and you won’t get any conduction on the distal end because there is nothing there. Decreased velocity of transmission for a demyelinating disorder.
How would sexual arousal look with a cervical spinal cord injury?
Reliant on reflexogenic pathway to induce sexual arousal. This means that touch to genitals will likely still elicit vasocongestion (erection).
How would sexual arousal in the case of a sacral injury?
A sacral injury may interfere with the reflexogenic pathways (S2-S4) so genital arousal would mostly be dependent on mental arousal. Touch to genitial would not elicit vasocongestion.
Explain male ejaculation: Branches of the nervous system involved, their spinal levels, the nerves, and the roles of each part
What areas of the spinal cord are indicated?
A: dorsal column
B: Dorsal horn (sensory)
C: lateral corticospinal tract
D: lateral spinothalamic tract
E: Ventral horn (motor)
