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Autonomic Nervous System RICHARD E. FREEMAN MD MPH 2013 Lock Haven University NERVOUS SYSTEM - REVIEW HOMEOSTASIS The body’s ability to maintain a stable, relatively constant condition through multiple dynamic equilibrium adjustment and regulation mechanisms. Divisions of the Nervous System Location Direction Control Action Structures NEUROTRANSMITTER Neurotransmitters endogenous chemicals that transmit signals from a neuron to a target cell (FREQUENTLY another neuron or muscle) across a synapse. Examples: Acetylcholine, epinephrine, norepinephrine, serotonin, dopamine etc THE SYNAPSE COMING AND GOING AFFERENT: ARRIVING from the SENSORS to THE CENTRAL NERVOUS SYSYTEM INCOMING EFFERENT: EXITING from the THE CENTRAL NERVOUS SYSTEM to the EFFEXORS OUTGOING ALL NERVES IN THE AUTONOMIC NERVOUS SYSTEM ARE EFFEFENT GANGLION VS PLEXUS Ganglia: mass of neuron cell bodies that interconnect and relay info via synapses Dorsal Root ganglia: afferent (sensory) Autonomic ganglia: efferent (motor) Basal ganglion: Brain-relay stations for multiple cerebral/cerebellar/thalamic/hypothalamic/brai n stem functions Examples: striatum, caudate nucleus, globus pallidum, substantia nigra, etc Plexus: intersecting and recombining nerve fibers- (major highway intersections) AGONIST VS. ANTAGONIST An agonist is a chemical that binds to cell (neuroreceptor) & triggers or stimulates a response by that cell. Epinephrine – Beta receptor stimulate- speeds up the heart Example: An antagonist blocks the action of an agonist either by blocking the receptor or causing the inverse (opposite) action of the agonist. Metoprolol – Beta Blocker- slows the heart rate Example: Somatic versus Autonomic Pathways ANS = 2 neurons span the distance from CNS to effectors • presynaptic neuron cell body in CNS -- brain or spinal cord • postsynaptic neuron cell body in a peripheral ganglion (not dorsal root ganglion) AUTONOMICGENERAL PROPERTIES General Properties of the ANS Motor (EFFERENT)system that controls visceral organs glands, cardiac and smooth muscle Regulates unconscious processes that maintain homeostasis ANS carries out its actions without our intent INVOLUNTARY TWO Divisions of the ANS SYMPATHETIC DIVISION: prepares body for physical activity (Flight or Fight) PARASYMPATHETIC DIVISION: calming affect on many body functions & assists in bodily maintenance (Rest and Digest) Central Control of Autonomic Function ANS is regulated by several levels of the CNS Limbic system connected to hypothalamus Hypothalamus (major visceral motor control center) Reticular Spinal formation & brainstem nuclei cord reflexes WILL BE MORE SPECIFIC LATER!! Visceral Reflexes Unconscious, automatic responses to stimulation 1. Receptors detect internal stimuli - 2. Afferent neurons (incoming) connect to interneurons (connecting) in the CNS 3. Interneurons synapse with efferent neurons (outgoing) 4. Efferent neurons carry motor signals to the effectors EFFECTORS— GLANDS, SMOOTH MUSCLE, CARDIAC MUSCLE, Visceral Reflex Arc EXAMPLE: Visceral Reflex to BLOOD PRESSURE CHANGES AUTONOMIC TONE AUTONOMIC TONE: normal rate of activity that represents the BALANCE of the two systems: Goal: Maintain Homeostasis ACCELERATOR AND BRAKE Effects of each system depend upon neurotransmitters released Sympathetic and Parasympathetic “Tone” the BASAL AND BALANCED rate of activity of each system this background activity allows for an increase or decrease in activity by a single system EXAMPLES: sympathetic tone normally causes about 50 % vasoconstriction increasing or decreasing “tone” can change vessel diameter parasympathetic tone provides background G.I. activity Sympathetic Tone and Vasomotor Tone Sympathetic division prioritizes blood vessels to skeletal muscles & heart in times of emergency. Blood vessels to skin vasoconstrict to minimize bleeding if injury occurs during stress or exercise. Dual Innervation Most of viscera receive nerve fibers from both parasympathetic & sympathetic divisions antagonistic effects oppose each other cooperative effects seen when 2 divisions act on different effectors to produce a unified effect Example: Sexual response Parasympathic: “Gets it up” – Erection Sympathetic: “Gets it out” - Ejaculation Normally, equally both divisions do not innervate an organ Control WITHOUT Dual Innervation Adrenal medulla, arrector pili muscles, some sweat glands & many blood vessels receive only sympathetic fibers Sympathetic tone is a baseline firing frequency Vasomotor tone can shift blood flow from one organ to another according to changing needs SYMPATHETIC NERVOUS SYSTEM NEUROTRANSMITTERS OF THE SYMPATHETIC SYSTEM Preganglionic: (short fiber) Acetylcholine (Nicotinic) Postganglionic: (long fiber) Norepinephrine Acetylcholine (rarely) Pathways of Preganglionic Sympathetic Fibers Efferent Pathways of Sympathetic NS Collateral Ganglia & Abdominal Aortic Plexus Adrenal Glands: Sympathetic ganglia Paired glands sit on superior pole of each kidney Cortex Mineralcorticoids: aldosterone Glucocorticoids: cortisol Androgens: testosterone Medulla: catecholamines Sympathoadrenal system the closely related functioning adrenal medulla and Symphathetic NS EPINEPHRINE, NOREPIPHRINE DOPAMINE ALL ACT LIKE HORMONES Stress Response mass sympathetic discharge increase in arterial pressure, heart rate and contractility, blood flow to muscles, blood glucose, metabolic rate, muscle strength, mental activity, blood coagulation prepares the body for vigorous activity need to deal with a life-threatening situation AKA - the fight or flight response Summary of Sympathetic Innervation BODY WALL: Effectors are innervated by sympathetic fibers found in spinal nerves (mixed with afferent fibers) FREQUENTLY travel WITH SOMATIC NERVES Piloerector muscles, sweat glands, vessels HEAD AND THORACIC CAVITY: Effectors are innervated by fibers in sympathetic nerves FREQUENTLY travel WITH CRANIAL NERVES ABDOMINAL CAVITY: Effectors are innervated by sympathetic fibers in splanchnic nerves. Summary of the end organ (effector) response to Sympathetic stimulation Apocrine/eccrine glands Eyes: Pupillary Lacrimal Endocrine: Adrenal cortex Adrenal medulla Digestive: Gallbladder Intestine Internal anal sphincter pancreatic glands salivary gland Lungs: Bronchial muscles Bronchial secretions Cardiovascular: Coronary arteries, skeletal muscle vessels, peripheral vascular bed, myocardium Urinary: Bladder wall muscle Internal urethral sphincter Reproduction: penis/clitoris internal muscle system Increased secretions Dilation Slight Increased secretion Increased secretion Increased secretion Relaxation Decreased peristalsis Contraction (pucker up!!) Decreased secretion Decreased secretion Dilation Reduced production Dilation (beta); Constriction (alpha) Dilation (beta); Constriction (alpha) Constriction Increased rate Relaxation Contraction No action Male ejaculation/female orgasm PARASYMPATHETIC SYSTEM Parasympathetic Nervous System Division of Autonomic NS Functions in harmony (opposition) to SNS Regulates visceral organs SLUDGE: salivation, lacrimation, urination, defecation, GI functions, emesis Pre and postganglionic neurons synapse close to the organ of innervation (unlike the SN where the ganglion is typically farther away from the target organ). Efferent Pathways of Parasympathetic NS Parasympathetic Functions of Cranial Nerves Oculomotor nerve (III) Facial nerve (VII) Glossopharyngeal (IX) Vagus nerve (X) Vagus Nerve Summary of the end organ effect of the Parasympathetic stimulation Apocrine/eccrine glands Eyes: Pupillary Lacrimal Endocrine: Adrenal cortex Adrenal medulla Digestive: Gallbladder Intestine Internal anal sphincter pancreatic glands salivary gland Lungs: Bronchial muscles Bronchial secretions Cardiovascular: Coronary arteries, skeletal muscle vessels, peripheral vascular bed, myocardium Urinary: Bladder wall muscle Internal urethral sphincter Reproduction: penis/clitoris internal muscle system No action Constriction Greatly increased secretion No action No action Contraction Increased peristalsis- defecation Relaxation Greatly increased secretion Greatly increased secretion Constriction Greatly increased No action No action No action Decreased contraction rate Contraction Relaxation Dilation of penile/clitoral vessel- erection No action AUTONOMIC NERVOUS SYSTEMNEUROTRANSMITTERS Neurotransmitters & Receptors Types of neurotransmitters released and types of receptors on target cells determines effects of ANS Sympathetic NS has longer lasting effects Many other substances also released as neurotransmitters enkephalin, substance P, neuropeptide Y, neurotensin, nitric oxide Cholinergic Receptors for ACh Acetylcholine binds to 2 classes of receptors nicotinic receptors (cholinergic receptor) Between pre and postganglionic neurons of BOTH sympathetic and parasympathetic NS muscarinic receptors (cholinergic receptor) Between postganglionic neurons and target organ in ALL parasympathetic neurons Between some postganglionic neurons and target organs in sympathetic NS ACETYLCHOLINE CHOLINESTERASE RASEHIBITORS NICOTINIC RECEPTORS FUNCTION A key function of nicotinic receptors is to trigger rapid neural and neuromuscular transmission. OPENING Na+ ChannelsRAPID DEPOLARIZATION AND REPOLARIZATION NICOTINIC RECEPTORS LOCATION Nicotinic receptors are found in: The somatic nervous system (neuromuscular junctions in skeletal muscles). BOTH sympathetic and parasympathetic nervous system (autonomic ganglia) .POST GANGLIONIC NEURON The central nervous system CLINICAL FINDINGS: NICOTINIC RECEPTOR STIMULATION SYMPATHETIC NERVOUS SYSTEM (due to ganglionic stimulation of the adrenal gland). Hyperglycemia, glycosuria, ketosis. Hypertension. Leukocytosis with a left shift. Mydriasis (pupillary dilation) in up to 13% of the cases. Sweating. Tachycardia, tachydysrhythmias. Urinary retention. NICOTINIC RECEPTOR STIMULATION (CHOLINESTERASE INHIBITOR) Monday Tuesday Wednesday Thursday Friday Mydriasis (pupillary dilation) Tachycardia Weakness Hypertension Fasciculations MUSCARINIC RECEPTORS MUSHROOM POISON Muscarinic receptors are located in the: PARASYMPATHETIC NERVOUS SYSTEM. Cardiac conduction system. Exocrine glands. Smooth muscles. Sympathetic nervous system. Sweat glands. Central nervous system. MUSCARINIC RECEPTORS Slower BUT response is prolonged May be excitatory or inhibitory. Do not affect skeletal muscles Do influence the activity of smooth muscle, exocrine glands, and the cardiac conduction system. MODULATE ONLY- DO NOT INITIATE (due to intrinsic electrical/mechanical rhythmic activity) MUSCARINIC RECEPTORS No channels; Receptor activates guanine nucleotide binding protein (G-protein) activates many intracellular activities MUSCARINIC ACTIONS CARDIAC EFFECTS. AV blocks, with escape rhythms. Bradycardia. Ventricular dysrhythmias. EXOCRINE GLAND ACTIVITY. Bronchorrhea. Hyperamylasemia. Lacrimation. Rhinorrhea. Salivation. SMOOTH MUSCLE ACTIVITY. Bladder stimulation, sphincter relaxation. Bronchospasm. Miosis (pupillary constriction), eye pain due to ciliary spasm. Nausea, vomiting, cramps, diarrhea Parasympathetic* (muscurinic) TOXIDROME SLUDGE Salivation Lacrimation Urination Defecation GI pain Emesis DUMBELS Defecation/Diaphoresis Urination Miosis (pupillary constriction) Bronchospasm and Bronchorrhea Emesis Lacrimation NEUROTRANSMITTERS OF THE SYMPATHETIC NERVOUS SYSTEMADRENERGICS (catecholamines) NOREPINEPHRINE HORMONE & NEUROTRANSMITTER Post ganglionic sympathetic neurons Adrenal medulla EPINEPHRINE HORMONE & NEUROTRANSMITTER Adrenal medulla Adrenergic Receptors for NE Norepinephrine binds to 2 classes of receptors Alpha (adrenergic) Beta (adrenergic) Beta 1 Beta 2 Adrenergic Receptors and Function Alpha Beta Vasoconstriction Vasodilation Iris Cardioacceleration Dilation Intestinal relaxation Pilomotor contraction Bladder Sphincter Contraction Increased myocardial strength Uterus relaxation Bronchodilation Glycogenolysis Bladder wall relaxation END ORGAN EFFECTS OF AUTONOMIC STIMULATION OR INHIBITION EYE SYMPATHETIC Meds: --pupillary dilation (mydriasis) phenylephrine, cocaine, epinephrine PARASYMPATHETIC--pupillary constriction and accommodation (focusing) of the lens Meds: pilocarpine – muscarinic receptor GLAUCOMA Dual Innervation of the Iris GLANDS OF THE BODY SYMPATHETIC stimulates the sweat glands PARASYMPATHETIC stimulate the nasal, lacrimal, salivary, and G.I. gland GI TRACT SYMPATHETIC has very little effect PARASYMPATHETIC stimulates muscle overall activity including G.I. smooth Enteric Nervous System Nervous system of the digestive tract Composed of 100 million neurons found in the walls of the digestive tract (no components found in CNS) Has its own reflex arcs Regulates motility of viscera and secretion of digestive enzymes and acid in concert with the ANS –peristalsis - sequential Enteric Nervous System HEART SYMPATHETIC increases the rate and contractility systemic (adrenal medulla) – epinephrine/norepinephrine and some direct SA Node PARASYMPATHETIC decreases heart rate Vagus Nerve-cholinergic AV node BLOOD VESSELS SYMPATHETIC Vasoconstriction-arterioles Raises blood pressure PARASYMPATHETIC some vasodilation SECTION PHARMOCOLOGY & THE AUTONOMIC NERVOUS SYSTEM ADRENERGIC OR SYMPATHOMIMETIC AGONISTS act like norepinephrine and epinephrine these drugs have an effect which is much more prolonged than that of either norepi or epi Phenylephrine/oxymetolazine stimulates alpha receptors Isoproterenol, stimulates both beta1 and beta2 receptors albuterol stimulates only beta2 receptors some drugs act indirectly by increasing the release of norepi from its storage terminals ephedrine, tyramine, and amphetamine ADRENOGENIC ANTAGONIST & SYMPATHOLYTIC synthesis and storage phentolamine and phenoxybenzamine Prazosin (Minipress) Blood pressure Terasosin (Hytrin) - alpha-1 blocker- BPH beta blockers guanethidine alpha blockers reserpine release from the nerve terminal drugs that block (antagonist) the effect of norepi and epi: antagonist beta1 and 2 - propranolol, beta1 - metoprolol ganglionic blockers ANS pharmacology PARASYMPATHOMIMETIC DRUGS CHOLINESTERASE INHIBITORS nicotine activates nicotinic receptors pilocarpine and methacholine activates muscarinic receptors, cause profuse sweating Donepezil (Aricept) Rivastigmine (Exelon)– Alzheimer’s neostigmine, pyridostigmine,and ambenonium potentiates the effect of acetylcholine ANTIMUSCARINIC DRUGS atropine and scopolamine blocks the effect of acetylcholine on effector cells . Nicotinic and muscarinic receptors (Choose ALL correct answers) A. Are both acetylcholine receptors. B. Have the same structure. C. Have different physiology. D. Have different functions. E. None of the above. When compared with the action of nicotinic receptors, muscarinic receptors: (Choose ALL correct answers) A. Are faster. B. Initiate rather than modulate smooth muscle activity. C. Have primarily parasympathetic effects on the peripheral nervous system. D. Stimulate sweating via the sympathetic nervous system. E. None of the above. Muscarinic receptors are found in: (Choose ALL correct answers) A. Skeletal muscle. B. Smooth muscle. C. Exocrine glands. D. Sweat glands. E. None of the above. . Cholinesterase inhibitor toxicity leads to the following clinical findings mediated by muscarinic receptors: (Choose ALL correct answers) A. Miosis (pupillary constriction). B. Bronchorrhea. C. Nausea. D. Bronchospasm. E. None of the above.