Autonomic nervous system

Autonomic nervous system
The autonomic nervous system Blue = parasympathetic Red = sympathetic
Latin	divisio autonomica systematis nervosi peripherici

The autonomic nervous system (ANS or visceral nervous system) is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions.^[1] The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils, micturition (urination), and sexual arousal. Whereas most of its actions are involuntary, some, such as breathing, work in tandem with the conscious mind.

It is classically divided into two subsystems: the parasympathetic nervous system (PSNS) and sympathetic nervous system (SNS).^[1][2] Relatively recently, a third subsystem of neurons that have been named 'non-adrenergic and non-cholinergic' neurons (because they use nitric oxide as a neurotransmitter) have been described and found to be integral in autonomic function, particularly in the gut and the lungs.^[3]

With regard to function, the ANS is usually divided into sensory (afferent) and motor (efferent) subsystems. Within these systems, however, there are inhibitory and excitatory synapses between neurons.

The enteric nervous system is sometimes considered part of the autonomic nervous system, and sometimes considered an independent system.

Anatomy

ANS innervation is divided into sympathetic nervous system and parasympathetic nervous system divisions. The sympathetic division has thoracolumbar “outflow”, meaning that the neurons begin at the thoracic and lumbar (T1-L2) portions of the spinal cord. The parasympathetic division has craniosacral “outflow”, meaning that the neurons begin at the cranial nerves (CN 3, CN7, CN 9, CN10) and sacral (S2-S4) spinal cord.

The ANS is unique in that it requires a sequential two-neuron efferent pathway; the preganglionic neuron must first synapse onto a postganglionic neuron before innervating the target organ. The preganglionic, or first, neuron will begin at the “outflow” and will synapse at the postganglionic, or second, neuron’s cell body. The post ganglionic neuron will then synapse at the target organ.

Sympathetic division

The sympathetic division (thoracolumbar outflow) consists of cell bodies in the lateral horn of spinal cord (intermediolateral cell columns) of the spinal cord from T1 to L2. These cell bodies are GVE (general visceral efferent) neurons and are the preganglionic neurons. There are several locations upon which preganglionic neurons can synapse for their postganglionic neurons:

• Paravertebral ganglia of the sympathetic chain (these run on either side of the vertebral bodies)
• Prevertebral ganglia (celiac ganglia, superior mesenteric ganglia, inferior mesenteric ganglia)
• Chromaffin cells of adrenal medulla (this is the one exception to the two-neuron pathway rule: synapse is direct onto cell bodies)

These ganglia provide the postganglionic neurons from which innervation of target organs follows. Examples of splanchnic (visceral) nerves are:

• Cervical cardiac nerves & thoracic visceral nerves which synapse in the sympathetic chain
• Thoracic splanchnic nerves (greater, lesser, least) which synapse in the prevertebral ganglion
• Lumbar splanchnic nerves which synapse in the prevertebral ganglion
• Sacral splanchnic nerves which synapse in the inferior hypogastric plexus

These all contain afferent (sensory) nerves as well, also known as GVA (general visceral afferent) neurons.

Parasympathetic division

The parasympathetic division (craniosacral outflow) consists of cell bodies from one of two locations: brainstem (Cranial Nerves III, VII, IX, X) or sacral spinal cord (S2, S3, S4). These are the preganglionic neurons, which synapse with postganglionic neurons in these locations:

• Parasympathetic ganglia of the head (Ciliary (CN III), Submandibular (CN VII), Pterygopalatine (CN VII), Otic (CN IX)
• In or near wall of organ innervated by Vagus (CN X), Sacral nerves (S2, S3, S4))

These ganglia provide the postganglionic neurons from which innervations of target organs follows. Examples are:

• The preganglionic parasympathetic splanchnic (visceral) nerves
• Vagus nerve, which wanders through the thorax and abdominal regions innervating, among other organs, the heart, lungs, liver and stomach

Sensory neurons

The sensory arm is made of “primary visceral sensory neurons” found in the peripheral nervous system (PNS), in “cranial sensory ganglia”: the geniculate, petrosal and nodose ganglia, appended respectively to cranial nerves VII, IX and X. These sensory neurons monitor the levels of carbon dioxide, oxygen and sugar in the blood, arterial pressure and the chemical composition of the stomach and gut content. (They also convey the sense of taste, a conscious perception). Blood oxygen and carbon dioxide are in fact directly sensed by the carotid body, a small collection of chemosensors at the bifurcation of the carotid artery, innervated by the petrosal (IXth) ganglion. Primary sensory neurons project (synapse) onto “second order” or relay visceral sensory neurons located in the medulla oblongata, forming the nucleus of the solitary tract (nTS), that integrates all visceral information. The nTS also receives input from a nearby chemosensory center, the area postrema, that detects toxins in the blood and the cerebrospinal fluid and is essential for chemically induced vomiting or conditional taste aversion (the memory that ensures that an animal which has been poisoned by a food never touches it again). All these visceral sensory informations constantly and unconsciously modulate the activity of the motor neurons of the ANS

Motor neurons

Motor neurons of the ANS are also located in ganglia of the PNS, called “autonomic ganglia”. They belong to three categories with different effects on their target organs (see below “Function”): sympathetic, parasympathetic and enteric.

Sympathetic ganglia are located in two sympathetic chains close to the spinal cord: the prevertebral and pre-aortic chains. Parasympathetic ganglia, in contrast, are located in close proximity to the target organ: the submandibular ganglion close to salivary glands, paracardiac ganglia close to the heart etc... Enteric ganglia, which as their name implies innervate the digestive tube, are located inside its walls and collectively contain as many neurons as the entire spinal cord, including local sensory neurons, motor neurons and interneurons. It is the only truly autonomous part of the ANS and the digestive tube can function surprisingly well even in isolation. For that reason the enteric nervous system has been called “the second brain”.

The activity of autonomic ganglionic neurons is modulated by “preganglionic neurons” (also called improperly but classically "visceral motoneurons") located in the central nervous system. Preganglionic sympathetic neurons are in the spinal cord, at thoraco-lumbar levels. Preganglionic parasympathetic neurons are in the medulla oblongata (forming visceral motor nuclei: the dorsal motor nucleus of the vagus nerve (dmnX), the nucleus ambiguus, and salivatory nuclei) and in the sacral spinal cord. Enteric neurons are also modulated by input from the CNS, from preganglionic neurons located, like parasympathetic ones, in the medulla oblongata (in the dmnX).

The feedback from the sensory to the motor arm of visceral reflex pathways is provided by direct or indirect connections between the nucleus of the solitary tract and visceral motoneurons.

Function

Sympathetic and parasympathetic divisions typically function in opposition to each other. But this opposition is better termed complementary in nature rather than antagonistic. For an analogy, one may think of the sympathetic division as the accelerator and the parasympathetic division as the brake. The sympathetic division typically functions in actions requiring quick responses. The parasympathetic division functions with actions that do not require immediate reaction. Consider sympathetic as "fight or flight" and parasympathetic as "rest and digest".

However, many instances of sympathetic and parasympathetic activity cannot be ascribed to "fight" or "rest" situations. For example, standing up from a reclining or sitting position would entail an unsustainable drop in blood pressure if not for a compensatory increase in the arterial sympathetic tonus. Another example is the constant, second to second modulation of heart rate by sympathetic and parasympathetic influences, as a function of the respiratory cycles. More generally, these two systems should be seen as permanently modulating vital functions, in usually antagonistic fashion, to achieve homeostasis. Some typical actions of the sympathetic and parasympathetic systems are listed below.

Sympathetic nervous system

Main article: Sympathetic nervous system

Promotes a "fight or flight" response, corresponds with arousal and energy generation, and inhibits digestion.

• Diverts blood flow away from the gastro-intestinal (GI) tract and skin via vasoconstriction.
• Blood flow to skeletal muscles and the lungs is enhanced (by as much as 1200% in the case of skeletal muscles).
• Dilates bronchioles of the lung, which allows for greater alveolar oxygen exchange.
• Increases heart rate and the contractility of cardiac cells (myocytes), thereby providing a mechanism for the enhanced blood flow to skeletal muscles.
• Dilates pupils and relaxes the ciliary muscle to the lens, allowing more light to enter the eye and far vision.
• Provides vasodilation for the coronary vessels of the heart.
• Constricts all the intestinal sphincters and the urinary sphincter.
• Inhibits peristalsis.
• Stimulates orgasm.

Parasympathetic nervous system

Main article: Parasympathetic nervous system

Promotes a "rest and digest" response, promotes calming of the nerves return to regular function, and enhances digestion.

• Dilates blood vessels leading to the GI tract, increasing blood flow. This is important following the consumption of food, due to the greater metabolic demands placed on the body by the gut.
• The parasympathetic nervous system can also constrict the bronchiolar diameter when the need for oxygen has diminished.
• Dedicated cardiac branches of the Vagus and thoracic Spinal Accessory nerves impart Parasympathetic control of the Heart or Myocardium.
• During accommodation, the parasympathetic nervous system causes constriction of the pupil and contraction of the ciliary muscle to the lens, allowing for closer vision.
• The parasympathetic nervous system stimulates salivary gland secretion, and accelerates peristalsis, so, in keeping with the rest and digest functions, appropriate PNS activity mediates digestion of food and indirectly, the absorption of nutrients.
• Is also involved in erection of genitals, via the pelvic splanchnic nerves 2–4.
• Stimulates sexual arousal.

Neurotransmitters and pharmacology

At the effector organs, sympathetic ganglionic neurons release noradrenaline (norepinephrine), along with other cotransmitters such as ATP, to act on adrenergic receptors, with the exception of the sweat glands and the adrenal medulla:

• Acetylcholine is the preganglionic neurotransmitter for both divisions of the ANS, as well as the postganglionic neurotransmitter of parasympathetic neurons. Nerves that release acetylcholine are said to be cholinergic. In the parasympathetic system, ganglionic neurons use acetylcholine as a neurotransmitter, to stimulate muscarinic receptors.
• At the adrenal cortex, there is no postsynaptic neuron. Instead the presynaptic neuron releases acetylcholine to act on nicotinic receptors.
• Stimulation of the adrenal medulla releases adrenaline (epinephrine) into the bloodstream which will act on adrenoceptors, producing a widespread increase in sympathetic activity.

The following table reviews the actions of these neurotransmitters as a function of their receptors.

Circulatory system

Heart

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
cardiac output	β1, (β2): increases	M2: decreases
SA node: heart rate (chronotropic)	β1, (β2) [4]: increases	M2: decreases
Atrial cardiac muscle: contractility (inotropic)	β1, (β2)[4]: increases	M2: decreases
at AV node	β1: increases conduction increases cardiac muscle automaticity [4]	M2: decreases conduction Atrioventricular block [4]
Ventricular cardiac muscle	β1, (β2): increases contractility (inotropic) increases cardiac muscle automaticity [4]	---

Blood vessels

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
vascular smooth muscle in general	α1:[5] contracts; β2:[5] relaxes	M3: relaxes [4]
renal artery	α1[6]: constricts	---
larger coronary arteries	α1 and α2[7]: constricts [4]	---
smaller coronary arteries	β2:dilates [8]	---
arteries to viscera	α: constricts	---
arteries to skin	α: constricts	---
arteries to brain	α1[9]: constricts [4]	---
arteries to erectile tissue	α1[10]: constricts	M3: dilates
arteries to salivary glands	α: constricts	M3: dilates
hepatic artery	β2: dilates	---
arteries to skeletal muscle	β2: dilates	---
Veins	α1 and α2 [11] : constricts β2: dilates	---

Other

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
platelets	α2: aggregates	---
mast cells - histamine	β2: inhibits	---

Respiratory system

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
smooth muscles of bronchioles	β2:[5] relaxes (major contribution) α1: contracts (minor contribution)	M3:[5] contracts

The bronchioles have no sympathetic innervation, but are instead affected by circulating adrenaline ^[4]

Nervous system

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
Pupil dilator muscle	α1: Contracts (causes mydriasis)	-
Iris sphincter muscle	-	M3: contracts (causes miosis)
Ciliary muscle	β2: relaxes (causes long-range focus)	M3: contracts (causes short-range focus)

Digestive system

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
salivary glands: secretions	β: stimulates viscous, amylase secretions α1: stimulates potassium secretions	M3: stimulates watery secretions
lacrimal glands (tears)	β: stimulates protein secretion [12]	---
juxtaglomerular apparatus of kidney	β1:[5] renin secretion	---
parietal cells	---	M1: Gastric acid secretion
liver	α1, β2: glycogenolysis, gluconeogenesis	---
adipose cells	β1,[5] β3: stimulates lipolysis	---
GI tract (smooth muscle) motility	α1, α2,[13] β2: decreases	M3, (M1) [4]: increases
sphincters of GI tract	α1,[5] α2,[4] β2: contracts	M3:[5] relaxes
glands of GI tract	no effect [4]	M3: secretes

Endocrine system

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
pancreas (islets)	α2: decreases insulin secretion from beta cells, increases glucagon secretion from alpha cells	M3[14][15]: increases secretion of both insulin and glucagon.[14][15]
adrenal medulla	N (nicotinic ACh receptor): secretes epinephrine and norepinephrine	---

Urinary system

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
Detrusor urinae muscle‎ of bladder wall	β2:[5] relaxes	M3:[5] contracts
internal urethral sphincter	α1:[5] contracts	M3:[5] relaxes

Reproductive system

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
uterus	α1: contracts (pregnant[4]) β2: relaxes (non-pregnant[4])	---
genitalia	α1: contracts (ejaculation)	M3: erection

Integumentary system

Target	Sympathetic (muscarinic and adrenergic)	Parasympathetic
sweat gland secretions	M:[5] stimulates (major contribution); α1: stimulates (minor contribution)	---
arrector pili	α1: stimulates	---

References

1. ^ ^{a b} "autonomic nervous system" at Dorland's Medical Dictionary
2. ^ "eMedicine/Stedman Medical Dictionary Lookup!". http://www.emedicine.com/asp/dictionary.asp?keyword=autonomic+division+of+nervous+system. Retrieved 2008-11-30. ^{[dead link]}
3. ^ "Nitric oxide is the endogenous neurotransmitter of bronchodilator nerves in humans Maria G. Belvisi, C. David Stretton, Magdi Yacouba, Peter J. Barnes". http://www.sciencedirect.com/science/article/pii/001429999290676U. 
4. ^ ^{a b c d e f g h i j k l m n} Rang, Dale, Ritter & Moore (2003). Pharmacology 5th ed.. Churchill Livingstone. p. 127. ISBN 0443071454. 
5. ^ ^{a b c d e f g h i j k l m} Page 37 in: Costanzo, Linda S. (2007). Physiology. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7311-3. 
6. ^ Renal alpha-1 and alpha-2 adrenergic receptors: biochemical and pharmacological correlations JM Schmitz, RM Graham, A Sagalowsky and WA Pettinger
7. ^ Coronary vasoconstriction mediated by alpha 1- and alpha 2-adrenoceptors in conscious dogs O. L. Woodman and S. F. Vatner
8. ^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.  Page 270
9. ^ Circulation & Lung Physiology I M.A.S.T.E.R. Learning Program, UC Davis School of Medicine
10. ^ 1A-Adrenoceptors mediate contractions to phenylephrine in rabbit penile arteries J S Morton1, C J Daly1, V M Jackson2 and J C McGrath1: "1A-ARs could be utilized to aid the erectile response in male erectile dysfunction sufferers by reducing vasoconstriction of the penile arteries"
11. ^ Elliott, J (1997). "Alpha-adrenoceptors in equine digital veins: Evidence for the presence of both alpha1 and alpha2-receptors mediating vasoconstriction". Journal of Veterinary Pharmacology & Therapeutics (Blackwell Publishings) 20 (4): 308–317. doi:10.1046/j.1365-2885.1997.00078.x. PMID 9280371. http://www.ingentaconnect.com/content/bsc/jvpt/1997/00000020/00000004/art00009;jsessionid=8lm5thggpj1x.alice?format=print. 
12. ^ Protein secretion induced by isoproterenol or pentoxifylline in lacrimal gland P. Mauduit, G. Herman and B. Rossignol
13. ^ Sagrada, A; Fargeas, MJ; Bueno, L., A; Fargeas, MJ; Bueno, L (1987). "Involvement of alpha-1 and alpha-2 adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat". Gut 28 (8): 955–959. doi:10.1136/gut.28.8.955. PMC 1433140. PMID 2889649. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1433140. 
14. ^ ^{a b} Page 47 in: Poretsky, Leonid (2010). Principles of diabetes mellitu. New York: Springer. ISBN 9780387098401. 
15. ^ ^{a b} Duttaroy, A.; Zimliki, C. L.; Gautam, D.; Cui, Y.; Mears, D.; Wess, J. (2004). "Muscarinic Stimulation of Pancreatic Insulin and Glucagon Release is Abolished in M3 Muscarinic Acetylcholine Receptor-Deficient Mice". Diabetes 53 (7): 1714–1720. doi:10.2337/diabetes.53.7.1714. PMID 15220195.  edit

External links

• Receptors of the heart: Mnemonic
• Overview at arizona.edu
• ANS Medical Notes on rahulgladwin.com
• Explanations on the ANS by Dyansys, Inc.