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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.
 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                            