Spinal Cord Injury and the Autonomic Nervous System
Provide a detailed diagram of the autonomic nervous system and discuss the effects a spinal
cord injury (complete section) at T4 would have on autonomic function upstream and
downstream of the injury?
Though Spinal cord injuries in popular culture connected to paralysis and loss of motor function, in fact, spinal cord injury leads to a loss of sensory, motor and autonomic functions and maladapative changes below the level of the injury.
The spinal cord is a highly organised segmented structure, essential for the conveyance of neural connection from the central nervous system to be communicated to the periphery. There are 8 Cervical, 17 Thoracic, 5 Lumbar and 5 Sacral segments, each uniquely corresponding to outflow to specific organ systems (See Figure 1).
In current clinical practice spinal cord injuries are classified via the loss of motor and sensory function , with only the lower limbs being affected termed paraplegia, while movement lost in both limb is termed quadriplegia. The ASIA impairment scale allows for the level of injury to be established with the severity being classified from A (severe - complete loss) - E (no impairment), however loss of autonomic nervous system is not taken into account.
All the sympathetic outflow is conserved to the spinal cord with the sympathetic chain/column being essential for the conveyance of sympathetic innervation. While the parasympathetic innervation in contrast, has a large part of its output via a cranial nerve X - the vagus nerve, though there is portion of parasympathtic outflow at the most caudal end of the spinal cord - the sacral segment.
The effect of spinal cord injury can be wide reaching with disruption of the sympathetic chain being responsible for dysregulation of cardiovascular functions (blood pressure, autonomic dysreflexia, cardiac remodelling), thermogeneisis, gut motility, sexual function and respiration amongst many others. Though there is tentative evidence of effect on fat stores, immune functions as well as development of metabolic syndrome.
There is great cardiovascular complications in SCI with spinal shock occuring immediately following injury with a loss of vasomotor tone resulting in an acute low hypotension with a increased risk of cardiac arrest. However over time this dearrangement of the cardiovascular system continues and along with respiratory disturbance, is the major contributor to mortality in SCI patients.
A complete injury at the Thoracic level T4 would render the patient paraplegic as the outflow of the alpha motor neurones supply to the lower limbs being at the lumbar segment of the spinal chord. This high thoracic SCI will result in vasoconstriction of splanchnic vasculature, which containts a high blood volume, and is at a critical level for the developing autonomic dyreflexia and orthostatic hypotension which is a major obstacle in the patient's rehabilitation.
With a complete injury at T4 there would be a loss of vasomotor tone, resulting in decrease in blood pressure. This can be visualised though the electrophysioloigcal method of human microneurography in which a very thin electrode is inserted into a peripheral nerve such as the peroneal nerve, where single and multiunit recording is possible. In SCI patients there is significantly reduced sympathetic activity in comparison to a normal test subject (Stjernberg et al., 1986), through there overtime there are compensatory mechanisms.
Autonomic dysreflexia (AD) is a potentially fatal illness (Andersson, 2004) which develops due to uncontrolled sympathetic response secondary to a noxious or non-noxious stimulant and is most commonly in injuries at T6 and above. It most occurs following a full bladder, kinked catherer, UTI, bowel distension, faecal impaction and tight clothing.
Symptoms include: Extreme hyper tension with a blood pressure of 300mmHg systolic, severe headache, bradycardia due to baroreceptor initiated vagal stimulation, upper body sweating as well as anxiety and panic attacks. The risk of such high blood pressure can include catastrophic outcomes like cereal vasuclature damage and retinal detachment
Potential mechanisms of AD include sprouting of primary afferent fibres, such as peptidergic nociceptive fibres, plasticity of interneuronal connection between afferent fibres and sympathetic preganglion neruones, as well as changes in the excitability of the neurones, such as altered membrane properties.
Though human microneurography studies have shown during AD there is not the expected increase in sympathetic firing rate and duration. There is also no evidence of an increased barrage of activity in the pre- and post- ganglion of the sympathetic chain.
In animal models using wire myography, cord trasected animals showed an increased neurovascular coupling with increased vascular tone as a response to electrical field stimulation in comparison to the sham animals (McLachlan and Brock, 2006). Leading the hypothesis of potential change at the neuroeffector level at pre-and post-junctional points of blood vessels. In the tail artery in animal models it has been shown that it is the effect of post-junctional effects with a increased sensitivity to K+ ions, though unfortunately this does not translate to the human condition. In the mesenteric artery - part of the splanchic bed- it has shown as pre-junctional enhancement effect, with a reduced effect of the NAD transporter 1. In further animal models with a T10 transection, the femoral artery showed a greater expression of alpha-1 adrenoceptors. However the femoral artery is said to virtually uninnervated while the T10 transection is much lower than the T6 and above threshold placed for the possible development of AD. Thus, further study is necessary in order to elucidate the exact mechanism for the cause of AD in order to develop therapies., as currently the management consists of avoiding the triggering stimulant, through for example timely emptying of the bladder, as well as nitroglycerin paste which can be locally applied to bring on blood vessel dilatation.
A patient with a T4 complete transection will overall have uninteruppted parasympathetic innervation however downstream of the injury, the parasympathetic outflow of the sacral spinal segment. Though gut motility is intrinsic and is overall under the domain of the enteric nervous system, sphincter relaxation in both the GI tract and the Urinary tract is under parasympathetic control and will be effected, and thus many SCI patient require catheterization. Sexual function which requires both parasympathetic and sympathetic innervation will be also effected. In men, the parasympathetic nervous system in required in order to elicit an erection via nitric oxide led vasodilation and sympathetic innervation is necessary for ejaculation to place. Thus for SCI patients desiring to start a family vibrostimulation is required in order to produce a semen sample.
Upstream of the injury arrhythmias are most common at injuries at the T1 level due to the loss of direct sympathetic innervation of the heart and thus bradycardia is the most common arrhythmia.
Due to the cervical ganglion still receiving uninterruptd input cardiac function though at first normal, over time with the lack of the carotid blood pressure reflex can lead cardiac remodelling with left ventricular hypertrophy in order to maintain blood pressure homeostasis. West et al., (2014) showed this phenomena with a T3 level transection using echocardiography showing a decrease in left ventricular diameter, cardiac spetum thickness increased though there was no change in the overall mass of the heart. Lujan et al., (2014) T4 transection histologically studied showed a converse increase in LV are and a thinnin of the myocardial layer, this histological findings were confirmed by the Riddell lab with T1 transected animals studied showing via echocardiography a similar eccentric hypertrophy of the cardiomyocytes. This can be attributes directly to a loss of sympathetic innervation of the heart, and with reduced activity and reduced load resulting in persistent hypotension leading to cardiac remodelling in order to compensate.
Orthostaic hypotension is also an effect of T4 complete section, as the compensatory mechanism of increased heart rate is not sufficient to account from the loss of vasomotor tone in the lower portion of the patient's body which is exacerbated when upright due to the effects of gravity.
cord injury (complete section) at T4 would have on autonomic function upstream and
downstream of the injury?
Though Spinal cord injuries in popular culture connected to paralysis and loss of motor function, in fact, spinal cord injury leads to a loss of sensory, motor and autonomic functions and maladapative changes below the level of the injury.
The spinal cord is a highly organised segmented structure, essential for the conveyance of neural connection from the central nervous system to be communicated to the periphery. There are 8 Cervical, 17 Thoracic, 5 Lumbar and 5 Sacral segments, each uniquely corresponding to outflow to specific organ systems (See Figure 1).
All the sympathetic outflow is conserved to the spinal cord with the sympathetic chain/column being essential for the conveyance of sympathetic innervation. While the parasympathetic innervation in contrast, has a large part of its output via a cranial nerve X - the vagus nerve, though there is portion of parasympathtic outflow at the most caudal end of the spinal cord - the sacral segment.
The effect of spinal cord injury can be wide reaching with disruption of the sympathetic chain being responsible for dysregulation of cardiovascular functions (blood pressure, autonomic dysreflexia, cardiac remodelling), thermogeneisis, gut motility, sexual function and respiration amongst many others. Though there is tentative evidence of effect on fat stores, immune functions as well as development of metabolic syndrome.
There is great cardiovascular complications in SCI with spinal shock occuring immediately following injury with a loss of vasomotor tone resulting in an acute low hypotension with a increased risk of cardiac arrest. However over time this dearrangement of the cardiovascular system continues and along with respiratory disturbance, is the major contributor to mortality in SCI patients.
A complete injury at the Thoracic level T4 would render the patient paraplegic as the outflow of the alpha motor neurones supply to the lower limbs being at the lumbar segment of the spinal chord. This high thoracic SCI will result in vasoconstriction of splanchnic vasculature, which containts a high blood volume, and is at a critical level for the developing autonomic dyreflexia and orthostatic hypotension which is a major obstacle in the patient's rehabilitation.
With a complete injury at T4 there would be a loss of vasomotor tone, resulting in decrease in blood pressure. This can be visualised though the electrophysioloigcal method of human microneurography in which a very thin electrode is inserted into a peripheral nerve such as the peroneal nerve, where single and multiunit recording is possible. In SCI patients there is significantly reduced sympathetic activity in comparison to a normal test subject (Stjernberg et al., 1986), through there overtime there are compensatory mechanisms.
Autonomic dysreflexia (AD) is a potentially fatal illness (Andersson, 2004) which develops due to uncontrolled sympathetic response secondary to a noxious or non-noxious stimulant and is most commonly in injuries at T6 and above. It most occurs following a full bladder, kinked catherer, UTI, bowel distension, faecal impaction and tight clothing.
Symptoms include: Extreme hyper tension with a blood pressure of 300mmHg systolic, severe headache, bradycardia due to baroreceptor initiated vagal stimulation, upper body sweating as well as anxiety and panic attacks. The risk of such high blood pressure can include catastrophic outcomes like cereal vasuclature damage and retinal detachment
Potential mechanisms of AD include sprouting of primary afferent fibres, such as peptidergic nociceptive fibres, plasticity of interneuronal connection between afferent fibres and sympathetic preganglion neruones, as well as changes in the excitability of the neurones, such as altered membrane properties.
Though human microneurography studies have shown during AD there is not the expected increase in sympathetic firing rate and duration. There is also no evidence of an increased barrage of activity in the pre- and post- ganglion of the sympathetic chain.
In animal models using wire myography, cord trasected animals showed an increased neurovascular coupling with increased vascular tone as a response to electrical field stimulation in comparison to the sham animals (McLachlan and Brock, 2006). Leading the hypothesis of potential change at the neuroeffector level at pre-and post-junctional points of blood vessels. In the tail artery in animal models it has been shown that it is the effect of post-junctional effects with a increased sensitivity to K+ ions, though unfortunately this does not translate to the human condition. In the mesenteric artery - part of the splanchic bed- it has shown as pre-junctional enhancement effect, with a reduced effect of the NAD transporter 1. In further animal models with a T10 transection, the femoral artery showed a greater expression of alpha-1 adrenoceptors. However the femoral artery is said to virtually uninnervated while the T10 transection is much lower than the T6 and above threshold placed for the possible development of AD. Thus, further study is necessary in order to elucidate the exact mechanism for the cause of AD in order to develop therapies., as currently the management consists of avoiding the triggering stimulant, through for example timely emptying of the bladder, as well as nitroglycerin paste which can be locally applied to bring on blood vessel dilatation.
A patient with a T4 complete transection will overall have uninteruppted parasympathetic innervation however downstream of the injury, the parasympathetic outflow of the sacral spinal segment. Though gut motility is intrinsic and is overall under the domain of the enteric nervous system, sphincter relaxation in both the GI tract and the Urinary tract is under parasympathetic control and will be effected, and thus many SCI patient require catheterization. Sexual function which requires both parasympathetic and sympathetic innervation will be also effected. In men, the parasympathetic nervous system in required in order to elicit an erection via nitric oxide led vasodilation and sympathetic innervation is necessary for ejaculation to place. Thus for SCI patients desiring to start a family vibrostimulation is required in order to produce a semen sample.
Upstream of the injury arrhythmias are most common at injuries at the T1 level due to the loss of direct sympathetic innervation of the heart and thus bradycardia is the most common arrhythmia.
Due to the cervical ganglion still receiving uninterruptd input cardiac function though at first normal, over time with the lack of the carotid blood pressure reflex can lead cardiac remodelling with left ventricular hypertrophy in order to maintain blood pressure homeostasis. West et al., (2014) showed this phenomena with a T3 level transection using echocardiography showing a decrease in left ventricular diameter, cardiac spetum thickness increased though there was no change in the overall mass of the heart. Lujan et al., (2014) T4 transection histologically studied showed a converse increase in LV are and a thinnin of the myocardial layer, this histological findings were confirmed by the Riddell lab with T1 transected animals studied showing via echocardiography a similar eccentric hypertrophy of the cardiomyocytes. This can be attributes directly to a loss of sympathetic innervation of the heart, and with reduced activity and reduced load resulting in persistent hypotension leading to cardiac remodelling in order to compensate.
Orthostaic hypotension is also an effect of T4 complete section, as the compensatory mechanism of increased heart rate is not sufficient to account from the loss of vasomotor tone in the lower portion of the patient's body which is exacerbated when upright due to the effects of gravity.
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