Physiological consequences of spinal cord transection

This section reflects mainly on the physiology of high spinal injury (i.e. something happening in the low C-spine). The reason for this bias in the plethora of interesting physiological effects which are observed, rather than any sort of clinical importance of the injury itself.

The topic of spinal cord injury has been investigated in several SAQs:

• Question 11 from the first paper of 2024
• Question 29 from the second paper of 2022
• Question 18.3 from the first paper of 2010
• Question 15 from the first paper of 2006
• Question 14 from the first paper of 2005
• Question 2c from the first paper of 2003
• Question 1a from the first paper of 2000
• Question 1b from the first paper of 2000

The canonical resource to answer this question would have to be Chapter 78 from Oh's Manual, Spinal injuries by Sumesh Arora and Oliver J Flower. There, on page 801 an extensive exploration of ICU management is carried out, with all the relevant systems covered.

In brief, one can summarise the effects of spinal cord transection in the form of a table:

The Physiological Consequences of Spinal Cord Injury

Respiratory consequences Decreased maximum tidal volume Rapid respiratory fatigue Vital capacity increases in the supine position Cardiovascular consequences Decreased peripheral vascular resistance Decreased preload Increased α-adrenoceptor responsiveness Autonomic dysreflexia Loss of postural homeostatic reflexes Bradycardia. Fixed cardiac output

Gastrointestinal consequences of spinal injury Decreased gastric transit, and acute gastric dilatation Paralytic ileus The "body cast syndrome" Stress ulceration following spinal cord injury Metabolic and endocrine consequences Inappropriate antiduiretic hormone secretion (SIADH) Hyperaldosteronism Insulin resistance Suxamethonium sensitivity Hypercalcemia, osteoporosis and renal calculi Hypothermia of spinal cord injury

Now, in great detail:

Respiratory consequences of high spinal cord transection

With damage to the spinal cord above the T1 level, intercostal and other chest wall muscles become paralysed, with the result that the diaphragm is now solely responsible for the respiratory effort. For a thin strap of muscle, this is a lot of work. Without the chest wall performing its notmal "bucke handle" excusion, the pattern of respiration becomes paradoxical, almost obstructed-looking. The patient gives the impression of breathing with their abdomen: the chest does not rise and fall, but the abdomen seems to heave with each respiratory effort.

The mechanical consequences of this are discussed in a 2007 article by Cardozo, and the lung mechanics of spinal cord injury patients are explored in a 2001 paper by Baydur and Adkins. There are several major issue to consider:

 

Decreased maximum tidal volume:

The chest wall no longer assists with lung expansion, and thus the only volume change you can expect is through the displacement of abdominal content by the diaphragm. This diminishes the maximum tidal volume. Similarly, the expiratory effort is an effort of the diaphragm alone; thus the spirometry findings in these people tend to demonstrate a restrictive pattern, with a small volume rapidly exhaled.

Rapid respiratory fatigue:

the diaphragm cannot generate a sustained effort in situations when tachypnoea is called for, for instance with exertion or in context of metabolic acidosis. The capacity to compensate for acidosis is thus very limited.

Vital capacity increases in the supine position.

The patients seem to breathe easier when supine, particularly if the diaphragm is alone in the generation of respiratory effort. The reaosn for this is thought to be greater stretch of the diaphragm, which places it into a position of increased mechanical advantage.

One might think that respiratory volumes shoudl increase with sitting upright (as is the case for most patients) - but in this case, the gravitational displacement of the abdominal contents plays a detrimental role. The abdominal contents in the quadriplegic patient sloshes around according to the whims of gravity - the abdominal wall muscles are paralysed and atonic, doing little to maintain the position of the abdominal organs. The downward stretch exerted by the displaced abdominal contents may also expand the total intrathoracic volume, but this action places the diaphragm into a position of disadvantage - in this postion, it is already halfway-descended. Thus, the diaphragm has little further travel available, and its contraction only expands the intrathoracic volume by a small proportion. This is a similar problem to the experience of COPD patients, who have a flattened diaphragm.

Cardiovascular consequences of quadriplegia

Much of what happens to the cardiovascular system following spinal cord injury is attributable to two factors: the abolition of descending sympathetic control, and the decreased metabolic requirement of denervated muscle. Excellent articles by Teasell et al and Conti, et al can be recommended.

"Spinal shock" and neurogenic shock

The concept of "spinal shock" is discussed elsewhere. Without extensively digressing on the etymological origins of this confusing term, "spinal shock" is the abrupt boycott of normal function by the insulted spinal cord,  and "neurogenic shock" is the haemodynamic consequences of an ungoverned circulatory system.  Neurogenic shock is central in the explanation of the cardiovascular consequences of spinal cord injury in the long term. Essentially, the total body sympathetic denervation which occurs with spinal shock is only short-lived, and as time progresses, the sympathetic nervous system recovers to some extent- but its recovery is patchy, disorganised and bizarre.

Decreased peripheral vascular resistance

Not only is the vascular smooth muscle tone decreased. The tonic contraction of muscles which is maintained under normal circumstances in the non-paraplegic individual is also lost, and this contributes to the overall decrease in afterload. Blood pressure may fall as a result. This is usually seen in injuries above T6; anything lower than this tends to preserve enough supraspinal sympathetic control to maintain the total peripheral vascular resistance. The reduction in resting systolic blood pressure correlates fairly linearly with the spinal cord level; i.e. the reduction in peripheral vascular resistance is proportional to the number of denervated blood vessels.

Decreased preload

There is greater pooling of blood in the maximally dilated venous capacitance vessels, and thus there is diminished venous return to the heart.

Increased α-adrenoceptor responsiveness

The α-adrenoceptors, in the absence of stimulus, become more numerous and thus the peripheral vessels respond more vigorously to infused noradrenaline. These patients tend to require very low doses of noradrenaline if they become septic. The hyperresponsiveness tends to take some weeks to months to develop, and the recently paralysed patient does not tend to exhibit this effect.

Autonomic dysreflexia

Because of the loss of strict sympathetic control, and because of the hyperproliferation of adrenoceptors, the "autonomic" reflex responses in these patients can be wildly exaggerated. For one, any vagal reflex will be amplified because of unopposed vagal action. Additionally, any sympathetic stimulation below the level of transection may lead to a wildly exaggerated reflex sympathetic response, with massive hypertension. Noxious stimuli, bladder distension, constipation, sexual stimualtion - all these can lead to an "autonomic storm". This was the subject of Question 11 from the first paper of 2024, which asked for the clinical signs, prevention strategies and management of uncontrolled dysreflexia. For the greatest amount of detail, one is referred to Sober-Williams et al (2024) and Krassioukov et al (2021): 

• Definition:
  • Defined as "an increase in systolic blood pressure of > 20 mmHg from baseline in response to noxious or non-noxious stimuli below the level of injury" (Wecht et al, 2021)
  • Characterised by hypertension that persists until the precipitating sensory stimulus is removed
  • Usually occurs with lesions above T6
  • Can be provoked by both painful and nonpainful (eg. even sexual) stimuli
• Epidemiology
  • Prevalence around 48%-91% of patients with spinal cord injury above T6.
• Clinical features:
  • Headache
  • Dizziness
  • Nausea
  • Shortness of breath
  • Visual disturbances
  • Palpitations
  • Facial flushing, nasal congestion and sweating above the spinal lesion (baroreceptor-mediated vasodilatation)
  • Cold clammy skin with piloerection below the lesion level (also with sweating)
  • "Autonomic conflict"- cardiac arrhythmias arising from competing massive sympathetic and concurrent vigorous parasympathetic activity
  • Hypertension is the dominant finding, and leads to complications, such as:
    • Myocardial ischaemia and pulmonary oedema
    • PRES and intracranial haemorrhage
    • Seizures
• Prevention strategies:
  • A - extubate as soon as able, as these patients will have frequent episodes of dysreflexia in reaction to the ETT
  • B - avoid noxious airway stimuli, eg. suctioning 
  • C- Keep the circulating volume in the lower body by raising the head of the bed
  • D - even though there is no pain sensation, analgesia helps prevent noxious stimuli from triggering the episodes 
  • E - Maintain normal electrolytes so as not to give the gut a chance to do an ileus
  • F - maintain good urine output, support good hydration, prevent urinary retention by intermittent catheterisation.
  • G - Maintain regular bowel regime with aperients and enemas (the goal is to prevent constipation)
• Management:
  • During a hypertensive crisis, 
    • Lower the legs and elevate the head (Trendelenburg position)
    • Check the usual suspects:
      • Tight binding clothes
      • Urinary catheter/bladder (retention?)
      • Bowels (constipation?)
      • Pain (give empirical analgesia)
    • Use short-acting titratable agents:
      • GTN patches or nitroglycerine paste (2%) onto the skin above the spinal level
      • Nifedipine and prazocin also sometimes used
      • Clonidine, hydralazine, labetalol, captopril, all are seen in the wild
  • Long term:
    • Botox injections
    • Intravesical capsaicin
    • Transurethral sphincterotomy
    • Sacral bladder denervation via dorsal rhizotomies 
    • Malone anterograde continence enema (MACE)

We should all be grateful to Michele Dowlman who has remarked that this above-lesion "baroreceptor-mediated vasodilatation" is far from intuitive, and needs to be unpacked further.  Consider the statement, “hypertension elicits baroreceptor-mediated reflex bradycardia and vasodilatation in regions under supraspinal control in an attempt to reduce blood pressure” from Sober-Williams et al (2025). A direct reading of this would suggest that the vagus is mediating the vasodilation, which is of course impossible, as there is basically no parasympathetic input into any of the vascular smooth muscle.  Of course, with a spinal lesion, there is basically no direct sympathetic input into any of the vascular smooth muscle either, below the level of the lesion. Those vessels are still attached to the sub-lesional sympathetic neurons and express α1 receptors, but they are entirely beyond central regulatory control, and respond only to circulating catecholamines and the random whims of the disconnected spinal preganglionic neurons. When this is understood, the following pattern becomes self-explanatory:

• When some kind of spinal autonomic reflex triggers them, the spinal preganglionic neurons produce an impressive spike of hypertension within the territory of their control by α1-mediated vasoconstriction.
• The heart is still within some central control, the fibres to the stellate ganglion taking their origin from around T1-T2, and so some relaxation of sympathetic output to the heart can still occur, giving the vagus a monopoly.
• The baroreceptors, being above the lesion, note this spike in pressure, and respond normally, by trying to slow the heart rate and dilate the arteriolar resistance vessels.
• However, because they are disconnected from much of the circulatory system, the influence of the baroreceptor response only extends over the sympathetic distribution above the lesion.
• Thus, baroreceptor-mediated vasodilation and vagally mediated bradycardia accompany the hypertensive crises of autonomic dysreflexia.

But one might point out that this should only be possible for those patients who still have some of their sympathetic nervous system connected to central regulation, i.e. those with a lesion below T1. The sympathetic fibres originating from the spinal cord emerge from the T1-L2 levels. A lesion above these might be expected to produce a situation where there is only dysreflexic hypertension and vagal bradycardia, as there is no vascular territory to vasodilate in response to the baroreflex.  Indeed,  Lujan & DiCarlo (2020), in a mouse model, demonstrated that bradycardia and hypotension were the dominant stable norm, and Osborn et al (1990) observed that chronically lesioned rats gradually transitioned to becoming tachycardic instead of bradycardic when their bladder was distended, i.e. the myocardium shared in the exaggerated sensitivity of the other sympathetic innervation targets, and this increased sympathetic effect had overcome the descending vagal input. A patient with a C-spine level of injury therefore presents a very different clinical picture to the patient with a mid-T spine lesion.

Loss of postural homeostatic reflexes

Obviously with the loss of the efferent limb of the baroreceptor reflex arc, one is unable to compensate for changes in blood pressure with changes in cardiac output. The result is an orthostatic hypotension; it is thought that the main contributor is the decrease in venous return due to pooling of blood in the viscera.

Bradycardia

If the spinal cord lesion is in the C-spine, chances are the sympathetic innervation of the heart is lost. The myocardium is thus under unopposed vagal control. The result is bradycardia. The baroreceptor reflexes still work, and receive blood pressure information from the aortic arch and carotid bodies, but because of the interrupted sympathetic chain, the heart cannot receive the instructions to go harder, and the vessels do not hear the call to squeeze. The stellate ganglion that innervates the heart is just anterior to the neck of the first rib, around C7-T1, so lesions above this tend to produce a cessation of sympathetic input into the heart rate. But the vagus is still attached, and with unopposed vagal tone the heart rate slows. 

Worse yet, manoeuvres which normally result in the simulation of the autonomic nervous system (such as suctioning of the trachea) will have an unopposed vagal response rather than a balanced sympathetic-parasympathetic response; the result is a potential for an embarassing vagally mediated asystolic arrest after routine tracheal care.

Fixed cardiac output

As a result of abolished sympathetic input, the cardiac output cannot increase in repsonse to stress or exercise. One is unable to compensate correctly for shock states, for anaemia, for any sort of physiological stimulus which would demand increased tissue oxygen delivery. The only way of manipulating cardiac output in these patients (without resorting to inotropes) is the modification of left ventrcular preload, by the increase of LV filling volume. The cardiac contractility should still be subject to normal Frank-Starling relationships.

Metabolic and endocrine consequences of quadriplegia

This topic is explored with exhausting attention to detail in a four-part series, published by Claus-Walker and Halstead in the early 1980s in the Archives of physical medicine and rehabilitation. The references for this can be found below. Instead of dutifully reciting every minor point, I will focus on what is relevant to the intensivist.

Inappropriate antiduiretic hormone secretion (SIADH)

The loss of sympathetic innervation, and the ensuing vasodilated state, tends to result in systemic hypotension. Perhaps the efferent arc of the baroreceptor reflex is impaired, but not the afferent arc. The posterior pituitary secretes vasopressin in response to this shock state, and in vast quantities. This causes renal water retention and hyponatremia. As time progresses and normotension is to some extent restored, so does the SIADH resolve - but some hyponatremia may persist, because it seems the spinal injury patients lose their normal diurnal rhytm of vasopressin secretion.

Hyperaldosteronism

This is related to the exaggerated action of the renin-agiotensin-aldosterone axis. The renal secretion of renin is normally subject to constant descending inhibition by the sympathetic nervous system. When this inhibition is abolished, the juxtaglomerular appartus of the kidney becomes wildly hyperactive, secreting insane amonts of renin into the circulation. The resulting "hyperangiotensinism" is not enough to produce hypertension, but the increase in aldosterone secretion is certainly enough to cause features of hyperaldosteronism in some individuals. Hypokalemia and hypernatremia may be produced as a consequence.

Insulin resistance

The combination of inactivity and muscle wasting leads to adiposity, and to insulin resistance. Almost half of spinal injury patients become type II diabetics as a consequence. Spinal cord injury thus results in increased postprandial insulin levels, and this increase is sustained for longer than it would be in intact patients, resulting in a "reacive hypoglycaemia" some hours after a meal.

This will not be noticed until it is very late, as the normal sympathetic response to hypoglycaemia is abolished. The normal response would be a sympathetic-driven increase in muscle gluconeogenesis, and decreased glucose uptake by the muscle tissue. In quadriplegic patients, this will not happen, and the high insulin levels will be unopposed. A way of managing this might be the reduction of carbohydrate intake, avoiding large carbohydrate-rich meals.

Suxamethonium sensitivity

As the muscultaure fo the body is denervated, the muscles - bereft of central neural tone, and starving for it - begin to reflexively sprout massive amounts of acetycholine receptors. These receptors are extruded onto cell membranes all over the place. They are just waiting for acetylcholine, or its equivalent. Imagine, as suxamethonium comes along and locks these channels open. Cations stream in both directions. The serum potassium rises precipitously. Cardiac arrest ensues, typically about 4 minutes after induction (just when you were about to sit down).

How high does the potassium go? The first such complications were noted in a 1970 article by Tobey et al. Though the full paper was inaccessible, the preview was tantalising; and we are all grateful for the contributions of Hrshee, a reader who defeated the paywall to bring us this graph:

Baffling features of this paper include the use of volunteers to receive an infusion of suxamethonium, at the conclusion of which one (the especially unlucky Patient Number Four) experienced about 100 seconds of cardiac arrest, when his potassium rose from 3.5 to about 14.0mmol/L.  The sacrifice of each participant is even greater if we consider that total blood sample required from each was in the order of 300-600ml. The increased sampling volume permitted some extended conclusions to be drawn from the data, including the interesting observation that the potassium values from the inferior vena cava for Patient Four were much higher then the SVC values, which would support the assertion that skeletal muscle was the main source of the extra potassium.

Fortunately, this effect is short-lived even without antihyperkalemic therapy, and the potassum dutifully returns into the intracellular compartment within 20 or so minutes. Subsequent authors have used this as a cautionary tale, to steer people away from using depolarising NMJ blockers in spinal cord injury patients.

Hypercalcemia, osteoporosis and renal calculi

Early on, people recognised that "recumbency" is an important factor in the genesis of urinary tract calculi. Disuse of bone results in bone wasting, and associated elevated alkaline phosphatase levels. The precise mechanisms for this are incompletely understood. Is it merely the loss of mechanical loading? Are pathyroid glands somehow involved? Parathyroid levels frequently remain normal in the face of extreme bone wasting. As bone is demineralised, serum calcium and phosphate levels increase, resulting in hypercalciuria and renal calculus formation. Huge lacerating calculi can form without being noticed by the denervated ureters, and presentation is typically delayed until the patient notices that they are passing frank hematuria through their IDC.

Hypothermia of spinal cord injury

To put correctly, the spinal injury patient develops "poikilothermia", which is the deregulation of body temperature control leading to abnormally raised core temperature in hot environments, and abnormally low temperature in cold environments. The main reason for this is the loss of sympathetic control. Consider how much of one's thermoregulatory function is the result of piloerection, sweating, and vasodilation or vasoconstriction. Without these mechanisms, one is unable to control how much of one's body heat one exchanges with the external environment. Robbed of such reflexes, the tetraplegic is limited to altering their thyroid hormone secretion as a means of temeperature regulation - which is obviously useless in the context of rapid changes.

Gastrointestinal consequences of spinal injury

According to a 1981 evaluation of 567 spinal injury cases, during the first month post injury, these complications consisted of ileus, gastric dilatation, the body cast syndrome, peptic ulcer disease, and pancreatitis. A more recent review article elaborates extensively on this topic.

Decreased gastric transit, and acute gastric dilatation

The severity of this seems to correlate with ascending level of spinal cord injury. Gastric emptying is impaired because of a loss of sympathetic control of autonomic reflexes. The normal response to oeseophageal distension is gastric relaxation (to receive food); however in the spinal trauma animal models this vagal reflex arc somehow becomes hyperactive, and leads to over-relaxation of the stomach. The lazy stomach refuses to proceed with normal peristalsis, and becomes filled with food material. The incidence of this is reported as 10%, at least for gastric dilatation of any clinical significance. The implications are serious - a dilated stomach and a lax lower oesophageal sphincter are a recipe for aspiration.

Paralytic ileus following spinal cord injury

The pooling of blood in the lower body tends to lead to intenstinal oedema, and thus makes the bowel heavier, with more resistance to normal peristalsis. However, this is not the whole picture. Control of evacuation is also lost, and no spinal cord–mediated peristalsis occurs, resulting in slow stool propulsion. Left to control the bowel all on its own, the myoenteric nervous system becomes disorganised, and this results in ileus early in the history of a spinal cord injury.

The body cast syndrome

This is the syndrome of acute gastric dilatation associated with the application of a full-body plaster cast, which is thankfully no longer practiced. One article from 1970 recalls a particularly high mortality rate from this syndrome, due to "pernicious vomiting" and aspiration. The mechanism of this syndrome is the obstruction of the duodenum by the superior mesenteric artery, which occurs when the normal fatty jacket is shed from the mesenteric root. Thus unprotected, the duodenum becomes squished between the superior mesenteric artery and the aorta - both fairly robust structures. The feeble duodenum is unable to squeeze food boluses past such an obstruction, and gastric dilatation is the result.

Stress ulceration following spinal cord injury

This seems to be a common complication early in the progress of this disease. Again, dysautonomia is probably to blame - particularly the unopposed vagal influence on the stomach, resulting in a forceful muscarinic stimulus of the parietal cells, which dutifulyl pump out vast amounts of hydrochloric acid.

In general, it seems to greatest risk of gastric ulceration is between the fourth and tenth day after the spinal injury. It seems later in the course of chronic spinal injury the lifetime risk of death from peptic ulcer perforation reverts to the normal population average.