Overview of autonomic control
The afferent nerves are shared by both the sympathetic and parasympathetic branches of the autonomic nervous system; the glossopharyngeal (CN IX) and vagal (CN X) nerves receive information from baroreceptors, chemoreceptors, and cardiopulmonary receptors regarding blood pressure. These afferent nerves both communicate to a central area – the nucleus tractus solitarius (NTS) in the brainstem – which then modulates blood pressure via efferent parasympathetic and sympathetic outputs.
The efferent pathways are:
- Parasympathetic effects
- NTS → Inhibition of sympathetic tone
- NTS → Vagal efferent output to the heart (AVN, SAN) to ↓ HR
- The parasympathetic system has direct minimal effect on SVR, primarily affecting haemodynamics by direct input on HR and inhibition of sympathetic tone
- Sympathetic trunk efferent pathways
- T1-T4/5 – HR and contractility
- T5-L2
- Splanchnic vascular bed (mesenteric, renal, hepatic)
- Adrenal medulla (T10–L1)
- Lower limb vasculature
- Pelvic vasculature
- This is the primary regulator of SVR
Neurotransmitters and receptors
Adrenergic (adreno-) receptors:
These are the receptors of the sympathetic nervous system that serve to increase heart rate, contractility, SVR and venous tone.
- β₁ receptors
- Located in the heart (SAN, AVN, ventricles).
- Increased HR and contractility.
- Can be stimulated by adrenaline and noradrenaline, and antagonised by beta blockers.
- β₂ receptors
- Located in vascular smooth muscle (particularly skeletal, coronary, lungs) and the lungs’ bronchial smooth muscle.
- Causes vasodilation of vessels, bronchodilation of lungs.
- Salbutamol or other beta agonists will bronchodilate. Noradrenaline will have negligible effects on vascular smooth muscle. Adrenaline will cause vasodilation at low doses, but higher doses override this vasodilation due to increased binding at post-synaptic alpha receptor sites, causing net vasoconstriction.
- α₁ receptors
- Located in Vascular smooth muscle of the arterioles and veins. Also in pupils, bladder, uterus.
- Vasoconstriction of arterioles (↑ SVR) and veins (↑ stressed volume). Will also cause pupillary dilation and urine retention.
- Noradrenaline and adrenaline bind to cause vasoconstriction. Alpha blockers such as prazocin and doxazosin are anti-hypertensives.
- α₂ receptors
- Located in the CNS and periphery (pre- and post-synaptic receptors)
- CNS – ↓ sympathetic outflow and sedation. Reduces CO and SVR to reduce BP. Also sedating effect.
- Peripheral
- Presynaptic receptors (at the sympathetic nerve endings) cause negative feedback to noradrenaline and reduce sympathetic outflow.
- Postsynaptic receptors (the vascular smooth muscles themselves) cause vasoconstriction – but need high dose to cause this.
- α₂-agonists such as clonidine and dexmetotomadine produce sedative and anti-hypertensive effects via effects on the CNS.
The different types of muscarinic receptors:
The parasympathetic ANS predominantly affects HR and atrial contractility, with negligible direct clinical effect on the systemic circulation.
- M2 receptors
- Located in the heart (SAN, AVN, atria)
- Agonism inhibits sympathetic tone in the heart, causing ↓ HR and ↓ atrial contractility
- M3 receptors
- Located on the endothelium (not smooth muscles) of blood vessels. Also smooth muscles of the lungs, pupils and GI tract.
- Cause bronchoconstriction, pupil constriction, GI motility. They are distributed in vascular beds and although cause vasodilation (via NO release), their haemodynamic effect is small.
Reflexes
There are a number of reflexes across the body that sense different information (such as stretch, pH, carbon dioxide) in order to maintain haemodynamic homeostasis.
Baroreceptors
Baroreceptors are stretch receptor cells located in the carotid sinus and aortic arch, which modulate heart rate, contractility and peripheral cardiovascular tone in response to stretch. The afferent nerves of the carotid sinus and aortic arch are the glosopharyngeal nerve (CN IX) and vagus nerve (CN X), respectively. They are integrated in NTS within the medulla, with efferent innervation via the sympathetic chain and vagus nerves. Increased sympathetic activity can increase vascular tone (a1), heart rate (β1) and contractility (β1), whilst the vagus nerve slows heart rate (M2).
- ↑ intravascular pressure (BP) → ↑ baroreceptor stretch → ↑ baroreceptor firing rate → ↑ vagal activity & ↓ sympathetic tone → ↓ HR ↓ vasoconstriction ↓ contractility.
Atrial stretch receptors
Bainbridge (atrial stretch) reflex describes a modest increase in heart rate that can occur during increased preload. Stretch receptors in the and atria respond by reducing vagal tone and increasing heart rate. Sinus arrhythmia may be explained by this reflex, where inspiration reduces intrathoracic pressure, increases preload and atrial stretch, leading to an increased the heart rate. Expiration increases intrathoracic pressure which opposes venous return, resulting in a transient slowing of the heart rate.
Baroreceptor vs atrial stretch receptor response:
The Bainbridge and Barorecepetor reflexes respond to increased stretch in opposite directions (reduced and increased vagal tone, respectively), and so the sum effect depends on which reflex response predominates. It would seem to follow that if increased atrial stretch causes tachycardia, then reduced stretch would likewise reduce the heart rate. However, clinically, in hypovolaemic states the baroreceptor reflex overides the bainbridge response by increasing the heart rate to maintain cardiac output. In hypervolaemic states, the bainbridge reflex seems to take precedence with an increased heart rate. It’s also been hypothesised that our possible evolution from a quadruped to biped state has increasingly selected baroreceptor response over bainbridge, to support postural changes from supine to upright.
Valsalva
Forced expiration against a closed glottis increases intrathoracic pressure to around 40 cmH2O. The (modified) vagal manoeuvre utilises the haemodynamic changes induced by valsalva to as a method for cardioversion of paroxysmal SVTs (AVNRT/AVRT).
- During the valsalva
- Compresses pulmonary vessels → squeezes blood into left heart → transient ↑ SV → transient ↑ MAP → reflex transient ↓ HR
- ↓ venous return to heart → ↓ SV → ↓ MAP → ↑ HR
- At release of valsalva
- Intrathoracic pressure relaxed → preload restored → HR still high → MAP overshoot → baroreceptor reflex → ↑ vagal stimulation → ↓ HR (this is mechanism for SVT cardioversion)
Chemoreceptors
Chemoreceptors are located in the periphery (carotid and aortic bodies) and centrally (medulla oblongata). Peripheral chemoreceptors share the same afferent pathways as their baroreceptor counterparts.
The peripheral chemoreceptors increase sympathetic tone in response to low PaO2, high PaCO2, or low pH, leading to tachycardia, increased vascular tone, and increased ventilation. Severe hypoxia triggers ↑ BP. The central chemoreceptors respond to CSF changes in CO2 and pH (but doesn’t detect O2 levels), leading to increased ventilation if these increase.
In clinical practice, however, there are instances where stimulation of chemoreceptors (via profound hypoxia, apnoea, reduced ventilation) may significantly increase vagal tone, causing bradycardia, AV block or even asystole. Bradycardia can be a pre-terminal sign in respiratory failure of infants, for example. In these cases of extreme hypoxia and/or ventilatory failure, bradycardia may be a primitive protective reflex to reduce myocardial oxygen demand, at the expense of cardiac output and systemic perfusion.
Trigeminal-cardiac reflex
The trigeminal-cardiac reflex is a neural arc responsible for the diving and occulo-cardiac reflexes. It is triggered by stimulation of the trigeminal (CN V) sensory nerves in the head, face and neck that can respond to multiple stimuli (chemical, mechanical, electrical). Afferent trigeminal nerves are integrated in the brainstem, with the efferent parasympathetic activation via the vagus nerve (CN X), as well as sympathetic inhibition.
Activation of this reflex can produce bradycardia or asystole, hypotension, cerebral vasodilation, and apnoea. Submersion or water to the face can trigger this theoretically protective diving reflex, which conserves cerebral oxygenation and prevents aspiration/drowning. Annoyingly, pressure on the globe or stretch of the occular muscles can also cause bradycardia or asystolic cardiac arrest, which opthalmology or maxfax surgeons will remain mindful of. Atropine can reverse this effect.
Intracranial baroreflex (Cushing reflex)
CPP = MAP – ICP.
Increased ICP results in reduced cerebral perfusion pressure. A compensatory response in the medulla triggers increased MAP to compensate. The rise in MAP stretches baroreceptors, triggering increased vagal tone and bradycardia. Direct pressure/ischaemia on the medulla also results in irregular respiration due to damage on the respiratory centres in the brainstem.
Spinal cord injury and blood pressure
Spinal cord injury can lead to massively dysregulated blood pressure.
Neurogenic shock: In the acute phase, spinal cord injury/transection affecting descending sympathetic tracts will disrupt sympathetic tone. Spinal shock is characterised by bradycardia and vasodilation that is typically poorly responsive to volume resuscitation (due to low venous tone preventing adequate stressed volume), and often requires vasopressors.
Vagal innervation is unaffected, leading to unopposed parasympathetic tone. This neurogenic shock can accompany the distinct but related pathology of spinal shock, which is a more global disruption of motor, sensory, and autonomic function below the level of the injury.
Autonomic dysreflexia is another derangement of blood pressure regulation that can occur chronically after spinal cord injury.
Injuries above the level of T6 mean that inhibitory descending control from the brainstem cannot reach sympathetic reflexes below.
Noxious stimuli such as bladder or bowel distension (which often accompanies spinal cord injury, with bladder and bowel dysfunction) can trigger massive reflex sympathetic activity. Sympathetic innervation from around T5-L2 causes vasoconstriction of the splanchnic vascular bed, as well as lower limb and pelvic vasculature. The large surface area of these vascular beds can massively raise SVR, causing uncontrolled hypertension due to loss of descending inhibition input.
This increased blood pressure is detected by the baroreceptors causing a reflex bradycardia via vagal efferents, but vasoconstriction cannot be inhibited by descending pathways in the baroreceptor reflex arc – due to disruption to the spinal pathways – resulting in runaway hypertension.