Anatomy of the parasympathetic nervous system

This chapter is relevant to Section M (i) of the 2017 CICM Primary Syllabus, which expects the exam candidates to "describe the autonomic nervous system, including anatomy", where the including anatomy specifically concerns the anatomy of the parasympathetic nervous system. For some weird reason this unimportant aspect of autonomic neurology was tested twice in the past papers:

• Question 1 from the first paper of 2017 (32% pass rate)
• Question 4 from the second paper of 2014 (0% pass rate)

From the comments made by the examiners, we can determine that "an outline of the relevant nerves" was necessary, and that the successful candidate would have to "named and located" all of the "various ganglia".  This is a strange expectation, as it is at odds with the future practice of intensive care trainees, during which none of their roles will ever require this. To reconcile this topic with the realities of critical care,  an attempt was made to inject relevance into the following recitation of anatomical facts by embedding fragments of clinically relevant information.

As with everything else about the autonomic nervous system, what qualifies a paper as "the best reference" here is brevity and clarity. The chapter that follows was constructed mainly using fragments from the 885-page 2023 edition of the Primer on the Autonomic Nervous System, which does not possess either quality. The best single reference is probably the first chapter from Jänig's  The Integrative Action of the autonomic nervous system (2022), as it can double up as an introduction to the rest of the autonomic nervous system, and is for some reason available for free from Cambrige University Press

Organisation of the parasympathetic nervous system

Whereas the sympathetic nervous system spreads out to widely supply the entire body from the T1-L1 thoracic nerve roots, the parasympathetic fibres come out to innervate very specific targeted organs via the cranial nerves and the sacral nerves. For the cranial nerves, the cell bodies of the preganglionic neurons sit in the cranial nerve nuclei of the brainstem, and for the sacral nerves they rest in the intermediolateral laminae (V-VII) of the second third and fourth sacral spinal cord segments, which is an analogous position to where the sympathetic pregangionic neurons live. The preganglionic fibres are long and myelinated, extending to various parasympathetic ganglia which sit closer to their target organs than the sympathetic ganglia. From these, unmyelinated postganglionic fibres extend to innervate their organ of interest, where the neurotransmission is cholinergic (muscarinic).

To depict this system in a way that might be comprehensible to the casual student is difficult. Diagrams of pathways quickly turn into incomprehensible spaghetti even in the hands of skilled artists. Worse yet are figures using living or preserved tissue specimens; each time, what must have started as a well-intentioned attempt to educate typically results in Cronenbergian nightmares such as this otic ganglion from Lovasova et al (2013):

Recoiling from this, the natural reaction of the horrified illustrator would be to trim away all possible levels of anatomical detail and to preserve only connections and locations of cell bodies as the most essential elements. This reductive approach simplifies the diagrams considerably, but loses so much information that there is no longer any benefit from using an image, as the same material could have been as easily presented in the form of a bullet-point list or a table. A tremendous example of such a table can be found in Bonica (1968), but it is much too large for the purposes of the CICM trainee, extending as it does over seven pages. A considerably trunkated version could be arranged as follows:

Preganglionic cell bodies	Nerves	Postganglionic cell bodies	Target organ
Cranial section of the parasympathetic nervous system
Edinger-Westphal nucleus of the midbrain	Oculomotor nerve	Ciliary ganglion	Eye (pupillary sphincter muscle and ciliary muscle)
Superior salivatory nucleus in the upper pons	Facial nerve, via the chorda tympani	Submandibular ganglion	Oral mucosa and the submandibular and sublingual salivary glands
Superior salivatory nucleus in the upper pons	Facial nerve (greater petrosal nerve)	Pterygopalatine gangion	Lacrimal glands and nasal mucosa
Inferior salivary nucleus in the lower pons	Glossopharyngeal nerve, via the lesser petrosal nerve	Otic ganglion	Parotid gland
Dorsal vagal nucleus of the medulla, and the nucleus ambiguus	Vagus	No named ganglia	Basically all organs in the chest and abdomen, down to the splenic flexure of the colon
Sacral section of the parasympathetic nervous system
Intermediolateral laminae	Pelvic splanchnic nerves (nervi erigentes)	Pelvic ganglia, distributed around the pelvic plexus	Distal intestine (descending colon and down) as well as urogenital organs

This probably represents some sort of minimum, and could be regarded as the shortest possible way to answer the anatomy section of the CICM SAQs. 

Central parasympathetic control structures

As with the sympathetic nervous system, the parasympathetic network is directed by the amygdala, insular cortex and anterior cingulate cortex, mostly via the hypothalamus and through glutamate-mediated and GABA-mediated neurotransmission. It is actually rather difficult to disentangle the control of the parasympathetic activity from the sympathetic, as this is the level at which they are integrated, and it is probably safest to refer to these control structures as broadly "autonomic" instead. Loewy's Central Regulation of Autonomic Functions (2011) is a definitive reference for this material, and the reader is left to decide for themselves whether they would want to burrow into the rich detail of physiology here, or whether it will suffice to list those cortical areas for exam purposes. Below these, other interesting structures include the periaqueductal gray where autonomic function is integrated with arousal and pain modulation, and some of the medullary structures that mediate cardiovascular autonomic reflexes (nucleus of the solitary tract, nucleus ambiguus, rostral ventrolateral medulla, etc). The anatomy of these is a lot less important than the physiology of the cardiac reflexes, which is discussed elsewhere.

Parasympathetic preganglionic neurons

The cell bodies of parasympathetic preganglionic neurons live in the brain stem and the spinal cord.The brainstem nuclei involved are:

• Edinger-Westphal nucleus of the midbrain, which controls the pupil via the third nerve, and which is responsible for the efferent arc of the pupillary light reflex. 
• Superior salivary nucleus in the pontine tegmentum, which innervates the lacrimal glands and some of the salivary glands, as well as the nasal mucosa
• Inferior salivary nucleus in the lowermost dorsal pons, at the junction with the medulla, which innervatres the parotid glands  
• Dorsal vagal nucleus in the medulla, which innervates seemingly everything in the chest and abdomen via the vagus nerve
• Nucleus ambiguus, also in the medulla, which needs a special mention because it sends parasympathetic fibres to the heart.

These are easy to list only because anatomists are kind and gentle people, inclined to ease the suffering of their students by committing forgivable crimes of oversimplification. The reality is a lot more messy. Anatomical positions of these preganglionic neurons are usually determined very indirectly, either by studies using stains that target cholinesterase, or by observing the neurodegeneration of structures that follows peripheral nerve lesions. Most serious researchers will freely admit that the resulting anatomical localisation is far from accurate ("sketchy" was the exact turn of phrase used by Gai & Blessing, 1996). For example, even though all kinds of textbooks confidently refer to the inferior and superior salivary nucleus, they may not actually exist. The cell bodies of these neurons may be scattered diffusely, rather than laying organised into neat nuclei. At least in the spinal cord the  preganglionic parasympathetic neuron cell bodies are well organised, residing in the intermediolateral laminae (V-VII) of the second third and fourth sacral spinal cord segments.  

Parasympathetic preganglionic nerve fibres

These long connections extend from the branstem nuclei and spinal cord to protrude towards their target organ. They are exclusively cholinergic and operate by activating postsynaptic N2 nicotinic receptors. There does not appear to be any rule of thumb with regards to their myelination or diameter, in the sense that a whole spectrum is represented throughout the parasympathetic network, ranging from extremely thin and slow (eg. C-fibres to the colon, propagating at 0.5m/s) to reasonably fast (8-10 m/s for the bladder and up to 15.5 m/s in the myelinated B-fibres of the vagus, such as the ones that supply the heart). One could generalise this by saying that mission-critical cardiovascular reflexes would need to run on faster fibres, whereas the genitals and alimentary tract could probably be make do with slower ones, as nothing the colon routinely does needs to be done in a hurry. 

Parasympathetic ganglia

No sooner then mocking illustrators for their futile efforts to depict the parasympathetic nervous system schematically, the author himself had also succumbed to this ambition, and produced this monstrous diagram. 

Like all the others before it, this diagram has not made anything clearer, other than the hubris of its author, and it has been left here mostly to shame him. Anyway:

To go through the ganglia, with links to authoritative resources:

• The ciliary ganglion  is a tiny structure approximately the size of a pinhead, in the posterior orbital fat
• The pterygopalatine ganglion is the largest of the four parasympathetic ganglia in the neck, and is located deep in the nose, posterior to the insertion of the middle nasal concha- relatively exposed, under a layer of thin mucosa. Its depth confers to it an invulnerability to rhinotillexomania, which means one should not be able to accidentally stimulate it. 
• The submandibular ganglion sits on the hypoglossus muscle, which is one of the muscles that tether the tongue to the hyoid bone. 
• The otic ganglion is a small structure under the foramen ovale, in the infratemporal fossa (where it is protected from pyring eyes by the zygomatic arch)
• The ganglia of the vagus are widespread, small, nameless, and forgettable. To give the reader an example, the tracheal ganglia sit on the adventital surface of the trachea, forming a disorganised mesh, and comprise of groups of no more than about 25 cells. In the heart, the ganglia are present mainly in the atria, nearest to the origins of the greater vessels and (obviously) close to the SA and AV nodes, according to Singh et al (1996).

At the ganglia, the synaptic junctions are cholinergic, and the receptors mediating transmission are N2 nicotinic receptors. These being good honest dependable cation channels, their transmission is rapid - the postsynaptic membrane depolarises and the action potential is conducted. 

Parasympathetic postganglionic fibres

With most of the hard work of conducting impulses now done by the preganglionic nerves, the postganglionic fibres need to do little other than slow-walk the action potential towards the cholinergic terminals at the effector organ. They are generally anything from one millimetre to a couple fo centimetres in length. For some reason unattractive for the histologist and anatomist, and their best descriptions come from the early half of the twentieth century, when people were still enthusiastic about anatomy and histology. Nonidez (1939) wrote, of the postganglionic vagal fibres in the cat heart, 

"many of them enter directly the walls of the atria and the interatrial septum, where they form extensive plexuses from which fibers are derived for the supply of the myocardium of these parts of the heart... In the sino-atrial node and more particularly in the atrioventricular node nerve terminations abound and they enmesh the muscle fibers characteristic of these portions of the conductive system. ...The smaller branches of the fibers end as rings of various sizes, , club-shaped endings and reticulated enlargements in contact with the surface of the muscle fibers."

These fibres are usually of the unmyelinated C-fibre type, as there is only a short distance to travel and saltatory conduction would not be necessary to speed up the rate of transmission. 

Parasympathetic nerve endings

Again from Nonidez (1939,

...The smaller branches of the fibers end as rings of various sizes, , club-shaped endings and reticulated enlargements in contact with the surface of the muscle fibers.

These nerve endings also release acetylcholine, but in this case it lands on muscarinic receptors which are G-protein coupled and therefore slow. They are still fast enough, however, to mediate baroreceptor responses, which occur over the timeframe of a single second.

Parasympathetic innervation of the tissues and organs

The parasympathetic nervous system and the sympathetic nervous system rarely overlap in their innervation, and most organs and tissues receive a dominant input from either one or the other. One way to systematically describe the distribution of parasympathetic output would be to list the nerves anatomically, but a) this was already done above, with mixed success, and b) most of the list would be all about the vagus. It would, perhaps, be better to list the parasympathetic contribution in terms of the tissues that are, and are not, innervated by this system. The tissues and organs that are managed exclusively by the parasympathetic nervous system are mostly secretory, and include:

• Salivary glands (which are minimally responsive to sympathetic stimulation)
• Gastric G-cells (which produce gastric acid)
• Mucus glands of the reproductive tract
• Lacrimal glands
• Nasopharyngeal mucus glands

In contrast, organs and tissues which receive basically no parasympathetic input include:

• The adrenal glands
• The majority of the blood vessels (except in the tumescent tissue of reproductive organs)
• The pilomotor muscles in the skin (hair follicles)
• Sweat glands