Autonomic Nervous System

Department of Anaesthesia University of Cape Town Autonomic Nervous System The autonomic nervous system (ANS) regulates the unconscious, involuntary control of automatic bodily functions; as opposed to the somatic nervous system that is under voluntary control. There is close integration between the ANS and the motor and sensory systems; ensuring that responses to sensory stimuli elicit appropriate motor responses. The autonomic nervous system can be influenced by higher centres, with some voluntary control over autonomic functions. Origins The autonomic nervous system is divided into two systems, the parasympathetic and the sympathetic. The parasympathetic nervous system outflow is cranio-sacral. The sympathetic nervous system outflow is thoraco-lumbar. Central control and integration between the systems is performed by the hypothalamus. Both systems consist of ganglia situated outside the central nervous system with pre- ganglionic fibres synapsing in the ganglia and sending signals onward via post-ganglionic fibres. Sympathetic nervous system The pre-ganglionic fibres of the sympathetic nervous system arise from the lateral horn of the spinal cord and frequently ascend or descend one or two segments within the spinal cord before they emerge along with the posterior segmental roots. These fibres then synapse in the ganglia of the sympathetic chain and give rise to long post-ganglionic neurons. The head is supplied by superior, middle and inferior (stellate) cervical ganglia, which are formed from pre- ganglionic fibres emerging from the first three thoracic segments. Sympathetic fibres frequently reach the end organs via the arterial blood supply to those organs. The adrenal medulla is a specialised sympathetic ganglion, in which the post-ganglionic fibres are modified into secretory cells rather than nerve fibres. Consequently, the output of this gland is hormonal rather than neuronal with noradrenaline being the dominant hormone (70 %) and most of the remainder adrenaline, with small amounts of dopamine. Figure 1. Sympathetic outflow from the spinal cord with associated ganglia Parasympathetic nervous system The parasympathetic nerve fibres arise from a cranio-sacral outflow, with the cranial outflow emerging with cranial nerves III, VII, IX, and X. Pre-ganglionic fibres arise from the brain stem, and these fibres are very long, with the parasympathetic ganglia being found close to the effector organs. Consequently, post-ganglionic fibres are usually short. Functions of the ANS are often organised as reflex arcs with outflow and inflow of these reflexes travelling along the same nerves. Figure 2. Parasympathetic outflow from the cranial and sacral segments respectively, showing the long pre-ganglionic and short post-ganglionic fibres. Autonomic nervous system Neurotransmitters in the ANS The only two transmitter substances of importance in the ANS are acetylcholine and noradrenaline. Acetylcholine (ACh) ACh is the neurotransmitter at all autonomic ganglia (nicotinic actions); at the post-ganglionic synapses in the post-ganglionic parasympathetic nerve endings and only at 2 sites in the sympathetic system: Apocrine sweat glands and vasodilatation in blood vessels of skeletal muscle (muscarinic actions). This latter action is physiologically unimportant. ACh is also the dominant neurotransmitter in the motor division of the somatic nervous system, supplying the neuromuscular junction. Nicotinic and muscarinic Receptors The cholinergic receptors are named nicotinic or muscarinic because of the substances that stimulate them in vivo i.e. nicotine and muscarine. The major response in the ganglia is nicotinic. Muscarinic transmission occurs at the post-ganglionic synapses of all parasympathetic nerve terminals and the sympathetic fibres to the sweat glands and vasodilators of skeletal muscle (mentioned above). Nicotinic receptors are also found in the somatic nervous system at the neuromuscular junction (NMJ). Noradrenaline This is the transmitter at most post-ganglionic sympathetic endings (excluding the exceptions mentioned above) and is divided into the well known and classification. The -adrenergic receptors are subdivided into 1 and 2 with the 2 receptors being mainly presynaptic and 1 receptors being on the arteriolar smooth muscle. receptors are subdivided into 1 (heart) and 2 (lungs), both of which are postsynaptic. Functions of the autonomic nervous system The sympathetic nervous system The sympathetic nervous system mainly mediates the “fight or flight” response and is important for stress responses and bodily defence mechanisms. What is the stress response? This is a neuro-humeral mechanism aimed at optimising circulation and metabolism for short-term survival and is a response designed to increase survival in the wild by optimising escape mechanisms. It is not, as frequently stated in the textbooks, aimed at perfusion of vital organs. See notes in the Fluid Chapter. The response involves haemodynamic changes redirecting blood flow to the “fight or flight” organs (heart, muscle and lungs) with sustained perfusion of the brain. Increased sympathetic tone decreases blood flow in all -adrenergically mediated vessels in the gut, kidney, liver and skin; while -agonist effects enhance blood flow in the coronaries and skeletal muscle and increase cardiac output. The response also involves mechanisms that maintain circulating blood volume. Redistribution of blood flow away from the kidneys decreases the glomerular filtration rate (GFR), but there is redistribution of intra-renal blood flow resulting in greater perfusion of the juxtamedullary nephrons which have long loops of Henlé and are specialised for salt and water retention. This leads to decreased salt and water clearance. Non-sympathetic components of the defence of blood volume include aldosterone release, enhancing sodium retention and antidiuretic hormone (ADH) release leading to increased water retention. Metabolic responses are aimed at directing glucose to “fight or flight” organs and involve the inhibition of insulin release through sympathetic mechanisms. The parasympathetic nervous system The parasympathetic system manages the “vegetative” functions associated with digestion and metabolism and include the “emptying” responses of the GIT (hence nausea and vomiting) and urogenital systems. It is thus the dominant system during periods of calm and rest or sleep. The sympathetic system only dominates during periods of stress, arousal, emotion or perceived danger; the “fight or flight” response. 2 Autonomic nervous system Organisation of the autonomic nervous system The ANS is organised is such a way that most organs receive both a sympathetic and parasympathtic supply. This means that the sympathetic post-ganglionic fibres are often very long (Figure 3). Figure 3. Diagram of the autonomic nervous system. 3 Autonomic nervous system The autonomic nerve supply from each system is usually balanced, with the overall effect depending on the relative dominance of each system: Sympathetic Parasympathetic Dilate pupil Constrict pupil The eye Relax ciliary muscle Constrict ciliary muscle Copious sweating No effect on sweating Sweat and Salivary Glands Inhibit secretions Copious GIT secretions ↓ peristalsis and tone ↑ peristalsis and tone Stomach ↑ Sphincter tone Relax sphincters Glucose released Slight ↑ glycogen synthesis Liver and Gall Bladder Gall bladder relaxed Constriction of biliary tree Bronchi dilated Bronchi constricted Lungs Pulmonary vessel constriction ↑ rate ↓ rate Heart ↑ force of contraction ↓ force of contraction Coronaries dilated The ANS and the heart The intrinsic rate of the heart is 100 - 120 beats min-1. This is determined by the inherent activity of the sino-atrial node. Changes in heart rate are a result of the balance between the sympathetic and parasympathetic activity. At rest in adults, vagal inhibition outweighs sympathetic stimulation and the normal heart rate is 70 - 80, whereas in children, the sympathetic system is dominant, resulting in a higher heart rate. A heart that has been transplanted would have had the vagus innervation completely transected during surgery; therefore patients with heart transplants have a HR of ± 110. The ANS and peripheral vasculature Blood vessels receive 1 receptor innervation and stimulation produces vasoconstriction through the innervation of arteriolar smooth muscle. Vasoconstriction is predominantly mediated by noradrenaline. Sympathetic “tone” is produced by intrinsic activity in these sympathetic nerves controlling the diameter of the vessels and is the major determinant of peripheral vascular resistance. Pharmacology of the autonomic nervous system The effects of drugs can be specific, precise, receptor-driven; or generalised, mediated through non- specific mechanisms affecting more global responses. The basic principal is that in organs innervated by both systems a specific desired effect can be achieved by either stimulating one system or blocking the other, e.g. heart rate is increased by either a sympathetic agonist or a parasympathetic antagonist. Drugs acting at ganglia The following examples illustrate some of the effects that drugs have on ganglionic activity. Ganglion blocking drugs are usually competitive antagonists at the post-synaptic nicotinic receptors. The only one in current use is trimetaphan camsilate (Arfonad®). This rarely used sulphonium compound is a competitive antagonist of the nicotinic action of ACh in the ganglia and blocks ganglionic transmission. Consequently, it

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