The Autonomic Nervous System (ANS) Dr. L. Al tmimi Academic year 2011-2012 This text is focused mostly on the anatomy and physiology of the Autonomic Nervous System (ANS), more specifically, about the two division of autonomic nervous system (sympathetic and parasympathetic), the different receptors related to this system and the neurotransmitters that stimulate these receptors. Nothing is mentioned about the pathology that affects this system or the commercial drugs that stimulate or inhibit these systems. Introduction The nervous system (NS) in general can be divided into central nervous system (CNS) and peripheral nervous system. The later can be more divided into somatic nervous system and autonomic nervous system (ANS). The somatic nervous system controls organs under voluntary control while the autonomic nervous system acts mainly below the level of consciousness and mostly not subject to voluntary control. The ANS has efferent and afferent nerve fibers, which transmit the impulses from the central nervous system to the peripheral organs and vice versa. Activation of Autonomic Nervous System In general activation of the ANS lead to the following effects in different organs Control of heart rate and force of contraction. Constriction and dilatation of blood vessels. Contraction and relaxation of smooth muscle in various organs. Visual accommodation, pupillary size. Secretions from exocrine and endocrine glands. Autonomic Nervous System division The ANS is divided into two divisions: The parasympathetic Nervous System (PNS) The sympathetic Nervous Systems (SNS) Both parts consist of myelinated preganglionic fibers that synapse with unmyelinated postganglionic fibers, and then innervate the effectors organ. Most organs are innervated by fibers from both systems except sweats glands and spleen are only innervated by SNS. The Parasympathetic Nervous System (PNS) Promotes a "rest and digest" response, supports calming of the nerves, return to regular function, and enhances digestion. The preganglionic outflow arises from the cell bodies of the motor nuclei of the cranial nerves III, VII, IX and X in the brain stem and from the 2 nd, 3 rd & 4 th sacral segments of the spinal cord. It is therefore also
known as cranio-sacral outflow. The cranial nerves III, VII and IX affect the pupil and salivary gland secretion. The Vagus nerve (X) carries fibers to the heart, lungs, stomach, upper intestine and ureter. The sacral fibers innervate the distal colon, rectum, bladder and reproductive organs. Preganglionic fibers pass directly to the organs. Postganglionic bodies lie near or within the viscera of the organ. There is a limited distribution of the postganglionic fibers with a ratio of postganglionic to preganglionic in many organs is 1:1 or 3:1 except in distal colon 8000:1. This lead to limited PNS effect, e.g. vagal bradycardia occurs without changes in intestinal motility. In physiological terms, the parasympathetic system is concerned with conservation and restoration of energy It causes a reduction in heart rate and blood pressure, facilitates digestion and absorption of nutrients, and consequently the excretion of waste products. Parasympathetic Nervous System Transmission The chemical transmitter at both pre and postganglionic synapses in the parasympathetic system is Acetylcholine (Ach). The synthesis of Ach occurs in the cytoplasm of nerve endings and is stored in vesicles in the presynaptic terminal. Ach performs its effect when it binds with its receptors. These receptors have been subdivided pharmacologically by the actions of the alkaloids into muscarinic and nicotinic receptors. Most transmissions occur in two stages: When a parasympathetic stimulation takes place, the preganglionic nerves release Ach at the ganglion, which acts on nicotinic receptors of postganglionic neurons. The postganglionic nerve then releases Ach to stimulate the muscarinic receptors of the target organ. The action of acetylcholine is terminated when the enzyme acetylcholinesterase degrades it. The Sympathetic Nervous System (SNS) Its general action is to mobilize the body's resources under stress; to induce the fightor-flight response. The cell bodies of the sympathetic preganglionic fibers are arising in the intermediolateral horns of the spinal segments T1-L3, the so-called thoracolumbar outflow. Activation of the SNS produces a diffused physiologic response (mass reflex) rather than discrete effects. This is because SNS postganglionic neurons outnumber the preganglionic neurons in an average ratio of 20:1 to 30:1.2. The preganglionic fibers travel a short distance in the mixed spinal nerve, and then branch off as white rami (myelinated) to enter the sympathetic ganglia. These sympathetic ganglionic chains are two paravertebral chains, lay anterolateral to the vertebral bodies and extend from the cervical to the sacral region. The preganglionic fibers may follow one of three courses: 1. Synapse with postganglionic fibers in ganglia at level of exit. 2. Path upward or downward in the trunk of the SNS chain to synapse in ganglia at other levels 3. Track for variable distances through the sympathetic chain and exit without synapsing to terminate in an outlying, unpaired, SNS collateral ganglion. Below is a summery of the SNS stimulation in different organs: On heart and circulation: Increase in heart rate, increase in force of heart contraction and also increase in blood pressure. The effects on the Lungs are: Bronchodilitation with increase in frequency of ventilation. On Skin: Increased sweating and piloerection. On blood: Mobilization of red blood cells from spleen and reduced blood clotting time.
On Gastrointestinal system: Decrease peristaltic activity and at the same time all the parasympathetic activities will be diminished. Sympathetic Nervous System Transmitter As PNS the preganglionic neurotransmitters of the SNS is Ach. Traditionally, the catecholamines epinephrine (EPI) and norepinephrine (NE) are considered the mediators of peripheral SNS activity. NE is released from localized presynaptic vesicles of nearly all postganglionic sympathetic nerves except the sweat glands. The SNS fibers ending in the adrenal medulla are preganglionic, and ACh is the neurotransmitter. Autonomic Nervous System Receptors Cholinergic receptors: Can be divided into Muscarinic and Nicotinic receptors. Muscarinic receptors: Are mostly found in the postganglionic junctions of the PNS. They exist also in other sites like the presynaptic membrane of sympathetic nerve terminals in the myocardium, coronary vessels, and peripheral vasculature that is way they called them adrenergic muscarinic receptors. Muscarinic receptors are mostly stimulated by muscarine however Ach can also stimulate these receptors. In general stimulation of the muscarinic receptors lead to bradycardia, negative inotropic effect, bronchoconstriction, miosis, salivation, gastrointestinal hypermotility, and increased gastric acid secretion. In addition to that stimulation of the adrenergic muscarinic receptors lead to inhibition of release of norepinephrine. Atropine blocks these receptors but has no effect on nicotinic receptors. So atropine may have a sympathomimetic effect through blocking of the muscarinic receptors and also vagal blockade. Some neuromuscular blockers like Pavulon (Pancuronium) may also induce tachycardia through this mechanism. Nicotinic receptors: Exist at the synaptic junctions of both SNS and PNS ganglia. Ach works also at these receptors together with nicotine the latter in low dose may induce a stimulation of the receptors while in high concentration will induce blockade effect. Nicotinic stimulation of the SNS ganglia produces hypertension and tachycardia by causing the release of EPI and NE from the adrenal medulla. Adrenergic receptors: These can be divided into β and α-receptors, which can be further subdivided into β1, 2 and 3 and α1 and 2 respectively. β-adrenergic receptors: Stimulation of β1 receptors lead to the following effects: On the heart: Increases myocardial contractility, Increases heart rate, Accelerates sinoatrial node and Accelerates ectopic pacemakers. On the kidney: stimulate the release of Renin and the metabolic effect: Fat cell lipolysis. While stimulation of β2 receptor lead to the following: Vasodilatation of the blood vessels, bronchodilation of the bronchus, relaxation of the bladder wall, relaxation of the pregnant uterus and encourage liver gluconeogenesis and glycogenolysis. Finally β3 receptors are thought to be responsible for enhancement of lipolysis in adipose tissue and have some central nervous system effect.
α-adrenergic receptors: These receptors have been further subdivided into clinically important classes α1 and α2 receptors. α1-adrenergic receptors: are found in the smooth muscle cells of the peripheral vasculature of the coronary arteries, skin, uterus, intestinal mucosa, and splanchnic beds. They serve as postsynaptic activators of vascular and intestinal smooth muscle as well as of endocrine glands. Their activation results in either decreased or increased tone, depending on the effector organ. The response in resistance and capacitance vessels is constriction, whereas in the intestinal tract it is relaxation. According to some evidence, α1 may also be available in the heart and may cause a positive inotropic effect and they may be responsible on arrhythmia during myocardial ischemia and reperfusion. So in summery their stimulation may lead to: coronary arteries constriction, intestinal vessels dilatation, positive inotropic effect on the heart, α2-adrenergic receptors: Stimulation of α2 in brain lead to antihypertension and sedation effect. While stimulation of the peripheral postsynaptic α2- receptors mediate constriction of smooth muscle, modulates large vessel tone, arteriolar and venous vasoconstriction. α2-receptors presynaptic effect opposes α1-receptor effect. Dopaminergic receptors: These receptors are localized in the CNS, blood vessels and postganglionic sympathetic nerves. It can be subdivided into DA1 and DA2. DA1 are postsynaptic receptors while DA2 are both pre and postsynaptic. The greatest numbers of DA1 postsynaptic receptors are found on vascular smooth muscle cells of the kidney and mesentery, but they can be also found in other systemic arteries like coronary, cerebral, and cutaneous arteries. The vascular receptors are, like the β2-adrenergic receptors, linked to adenylate cyclase and mediate smooth muscle relaxation. Activation of DA1 produces vasodilatation, increasing blood flow to these organs. Stimulation of DA2 presynaptic appears similar to the α2-adrenergic presynaptic receptors, inhibit NE release and lead to vasodilatation. While stimulation of DA2 postsynaptic receptors lead to vasoconstriction. DA receptors in the hypothalamus are involved in prolactin release. Parkinson disease may occur when the DA neurons that lies in substantia nigra, are degenerated. Another well-known central action of DA is stimulation of the chemoreceptor trigger zone of the medulla, producing nausea and vomiting. DA antagonists such as haloperidol and droperidol are clinically effective in countering this action. There is still doubt if dopaminergic receptors also are present in the myocardium. Adenosine Receptors: Adenosine produces inhibition of NE release. The effect of adenosine is blocked by caffeine, theophylline and other methylxanthines. The physiologic function of these receptors may be the reduction of sympathetic tone under hypoxic conditions when adenosine production is enhanced. As a consequence of reduced NE release, cardiac work would be decreased and oxygen demand reduced. Adenosine has been effectively used to produce controlled hypotension. Stimulation of adenosine receptors laying in the central nervous system help regulating the release of other neurotransmitters such as dopamine and glutamate
Serotonin receptors: Serotonin or also called 5-hydroxytryptamine (5-HT) is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system. The serotonin receptors are G protein-coupled receptors and ligand-gated ion channels that mediate both excitatory and inhibitory neurotransmission. They have influence on various biological and neurological processes such as aggression, anxiety, memory, mood, nausea, sleep, and thermoregulation. A widely use antiemetic drug called Zofran serotonin 5-HT3 receptor antagonist is an example of the drugs that antagonize the serotonin receptors. Another example is antidepressants medications like selective serotonin reuptake inhibitors (SSRIs) that are widely used now a day in treating of depression. An example of these drugs is Cipramil. Last but not least are the prostaglandin E2 receptors. Still to be read together with the pharmacology of autonomic nervous system in the Paul G. Barash Clinical Anesthesia, 6th edition CHAPTER 15. References: Paul G. Barash. Clinical Anesthesia, 6th edition. G Edward Morgan. Clinical Anesthesiology 2nd edition.