Introduction to the Autonomic Nervous System

Homeostasis : Marc Imhotep Cray, M.D. 2006 1 Homeostasis The physiologic process of maintaining an internal environment compatible with normal health. Autonomic reflexes maintain set-points and modulate organ system functions in pursuit of homeostasis.

Autonomic Reflexes : Marc Imhotep Cray, M.D. 2006 2 Autonomic Reflexes Afferent fibers from periphery to CNS CNS integration Hypothalamus Thalamus Cortex Medulla Spinal cord Efferent fibers from CNS to pheriphery

Neurotransmitters : Marc Imhotep Cray, M.D. 2006 3 Neurotransmitters Chemicals synthesized and stored in neurons Liberated from axon terminous in response to action potentials Interact with specialized receptors Evoke responses in the innervated tissues

Efferent Autonomic Nerves : Marc Imhotep Cray, M.D. 2006 4 Efferent Autonomic Nerves Innervation of smooth muscle, cardiac muscle, and glands Preganglionic neuron Peripheral ganglion - axodendritic synapse Postganglionic neuron(s) Effector organ(s) Pre Ganglion Effector organ

Anatomic Divisions of the ANS : Marc Imhotep Cray, M.D. 2006 5 Anatomic Divisions of the ANS Parasympathetic Preganglionic axons originate in the brain, and sacral spinal cord Peripheral ganglia are near, often within, the effector organs Ratio of postganglionic-to-preganglionic axons is small, resulting in discrete responses Sympathetic Preganglionic axons originate in the thoracolumbar cord Peripheral ganglia are distant from the effector organs Ratio of post-to-preganglionic axons is large, resulting in widely distributed responses

Schematized Anatomic Comparison : Marc Imhotep Cray, M.D. 2006 6 Schematized Anatomic Comparison Pre Ganglion Effector organs Post Thoracic or lumbar cord Sympathetic

Somatic Nervous System : Marc Imhotep Cray, M.D. 2006 7 Somatic Nervous System Efferent innervation of skeletal muscle No peripheral ganglia Rapid transmission, discrete control of motor units Any spinal segment Motor neuron Striated muscle

Neurochemical Transmission in the Peripheral Nervous System : Marc Imhotep Cray, M.D. 2006 8 Neurochemical Transmission in the Peripheral Nervous System Cholinergic nerves Acetylcholine is the neurotransmitter Locations Preganglionic neurons to all ganglia Postganglionic, parasympathetic neurons “Preganglionic” fibers to adrenal medulla Postganglionic, sympathetic neurons to sweat glands in most species Somatic motor neurons

Cholinergic Neurotransmission : Marc Imhotep Cray, M.D. 2006 9 Cholinergic Neurotransmission Sympathetic

Neurochemical Transmission in the Peripheral Nervous System : Marc Imhotep Cray, M.D. 2006 10 Neurochemical Transmission in the Peripheral Nervous System Adrenergic nerves Norepinephrine is the neurotransmitter Locations Postganglionic, sympathetic axons

Adrenal Medulla : Marc Imhotep Cray, M.D. 2006 11 Adrenal Medulla Presynaptic nerves are cholinergic Medullary cells synthesize and release two, related catecholamines into the systemic circulation Epinephrine (adrenaline) Norepinephrine Epi and NE stimulate adrenergic sites

Adrenal Medulla : Marc Imhotep Cray, M.D. 2006 12 Adrenal Medulla Cholinergic neuron Adrenal medulla Epi and NE released into systemic circulaton Denotes ACh

ACh Synthesis, Release, and Fate : Marc Imhotep Cray, M.D. 2006 13 ACh Synthesis, Release, and Fate Synthesized from choline and acetyl-CoA Released in response to neuronal depolarization (action potential) Calcium enters the nerve cell Transmitter vessicles fuse with cell membrane ACh released by exocytosis Inactivated by acetylcholinesterase (AChE)

NE Synthesis, Release, and Fate : Marc Imhotep Cray, M.D. 2006 14 NE Synthesis, Release, and Fate Catecholamine - synthesized in a multistep pathway starting with tyrosine Released by exocytosis in response to axonal depolarization Duration of activity primarily limited by neuronal reuptake Minor metabolism by synaptic monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT)

Receptors : Marc Imhotep Cray, M.D. 2006 15 Receptors Specialized proteins that are binding sites for neurotransmitters and hormones Postsynaptic cell membranes (neurotransmitters) Cell nucleus (steroid hormones) Linked to one of many signal transduction mechanisms

Ligand-Receptor Interactions : Marc Imhotep Cray, M.D. 2006 16 Ligand-Receptor Interactions Complementary conformations in 3 dimensions Similar to enzyme-substrate interactions Physiologic interactions are weak attractions H-bonding, van der Waal’s forces Drug mechanisms Agonists - bind and activate receptors Antagonists - bind but DO NOT activate receptors

Cholinergic Receptors : Marc Imhotep Cray, M.D. 2006 17 Cholinergic Receptors Activated by ACh and cholinergic drugs Anatomic distribution Postganglionic, parasympathetic neuroeffector junctions All autonomic ganglia, whethe parasympathetic or sympathetic Somatic neuromuscular junctions

Cholinergic Receptor Locations : Marc Imhotep Cray, M.D. 2006 18 Cholinergic Receptor Locations Sympathetic

Cholinergic Receptor Subtypes : Marc Imhotep Cray, M.D. 2006 19 Cholinergic Receptor Subtypes Muscarinic Postganglionic, parasympathetic, neuroeffector junctions Nicotinic Distinction of two different subtypes Ganglia - type I or type G Neuromuscular junctions - type II or type M

Cholinergic Receptor Subtype Locations : Marc Imhotep Cray, M.D. 2006 20 Cholinergic Receptor Subtype Locations Sympathetic N1 M N1

Adrenergic Receptors : Marc Imhotep Cray, M.D. 2006 21 Adrenergic Receptors Activated by NE, Epi, and adrenergic drugs Anatomic distribution Postganglionic, sympathetic, neuroeffector junctions Subtypes Alpha-1, 2; Beta-1, 2, 3

Adrenergic Receptor Locations : Marc Imhotep Cray, M.D. 2006 22 Adrenergic Receptor Locations Sympathetic

Functional Significance of the Autonomic Nervous System : Marc Imhotep Cray, M.D. 2006 23 Functional Significance of the Autonomic Nervous System Organ system integration Parasympathetic Discrete innervation Energy conservation Sympathetic Highly distributed innervation, global resonses Energy expenditure Fight or flight responses

Functional Significance of the Autonomic Nervous System : Marc Imhotep Cray, M.D. 2006 24 Functional Significance of the Autonomic Nervous System Dual innervaton Organ responses moderated by both parasympathetic and sympathetic influences Parasympathetic dominant at rest Balance of opposing neurologic influences determines physiologic responses

Introduction to Autonomic and Somatic Pharmacology : Marc Imhotep Cray, M.D. 2006 25 Introduction to Autonomic and Somatic Pharmacology Some drugs evoke effects by interacting with receptors Affinity Efficacy or (synonym) Intrinsic activity Agonists Mimic physiologic activation Have both high affinity and efficacy Antagonists Block actions of neurotransmitters or agonists Have high affinity, but no efficacy Often used as pharmacologic reversal agents

Alpha-1 Adrenergic Receptor : Marc Imhotep Cray, M.D. 2006 26 Alpha-1 Adrenergic Receptor Vascular smooth muscle contraction Arterioles, veins Increased arterial resistance Decreased venous capacitance Agonists support systemic blood pressure Increased resistance Redistribution of blood toward heart, increased cardiac output Antagonists decrease blood pressure Iris Pupillary dilation (mydriasis)

Alpha-2 Adrenergic Receptor : Marc Imhotep Cray, M.D. 2006 27 Alpha-2 Adrenergic Receptor Vasoconstriction Modulation of NE release Presynaptic receptors on axon terminous Spinal alpha-2 receptors mediate analgesia Agonists used clinically as epidural and spinal analgesics Sedation

Beta-1 Adrenergic Receptor : Marc Imhotep Cray, M.D. 2006 28 Beta-1 Adrenergic Receptor Exclusive to myocardium Agonists Increase HR, contractility, and impulse conduction speed May be arrhythmogenic Antagonists Decrease HR, contractility, and impulse conduction speed Used clinically as antiarrhythmics

Beta-2 Adrenergic Receptor : Marc Imhotep Cray, M.D. 2006 29 Beta-2 Adrenergic Receptor Vascular smooth muscle in skeletal muscle Agonists evoke active vasodilation, increased blood flow Bronchial smooth muscle Agonists evoke bronchodilation, decreased airway resistance

Muscarinic Cholinergic Receptor : Marc Imhotep Cray, M.D. 2006 30 Muscarinic Cholinergic Receptor Myocardium Agonists decrease HR and AV conduction velocity Antagonists used clinically to increase HR and facilitate AV conduction in heart block Iris sphincter muscle Agoinists evoke pupillary constriction (miosis) Antagoinists evoke mydriasis Gastrointestinal tract Agonists increase peristalsis and relax sphincters Urinary bladder Agonists evoke urination Detrusor muscle (bladder) contraction Trigone (sphincter) relaxation

Opioid-Induced Bradycardia : Marc Imhotep Cray, M.D. 2006 31 Opioid-Induced Bradycardia Opioids used as anesthetic premedications Oxymorphone, morphine Sedation, analgesia Stimulation of central parasympathetic nuclei Vagal stimulation evokes bradycardia Muscarinic antagonists compete with ACh at sino-atrial node Atropine, glycopyrrolate

Skeletal Muscle Paralysis : Marc Imhotep Cray, M.D. 2006 32 Skeletal Muscle Paralysis Facilitate manipulation of a surgical field Extraocular muscles for intraocular surgery Diaphragmatic paralysis for thoracic or abdominal surgery Nicotinic type 2 receptor Competative antagonists block ACh Atracurium, pancuronium Reversal of paralysis Restore spontaneous ventilation Acetylcholinesterase inhibitors Neostigmine, edrophonium Muscarinic effects Sinus arrest Blocked by muscarinic antagonists