THE AUTONOMIC NERVOUS SYSTEM

Transcription

1 I propose the term 'autonomic' nervous system for the sympathetic system and the allied nervous system of the cranial and sacral nerves and for the local nervous system of the gut. (John Newport Langley, 1898) Judit Rosta 1 11 October 2017 Evening Seminar Notes-Physiology

2 THE NERVOUS SYSTEM Introduction THE NERVOUS SYSTEM - DIVISIONS Structural divisions: Central nervous system (CNS) Peripheral nervous system (PNS) Efferents (motoric function) Afferents (sensory function) Interneurons Functional divisions: AUTONOMIC ( automatic control ) SOMATIC ( that we control ) Enteric Sympathetic (efferents) Parasympathetic Motoric (efferents) Sensory (afferents) Smooth muscle Cardiac muscle Gland cells Skeletal muscles Chemical, tactile, and visual signals 2 Evening Seminar Notes-Physiology 2

3 THE NERVOUS SYSTEM History "I propose the term 'autonomic nervous system'... The involuntary system: sympathetic ganglia independent of central connections named the vegetative nervous system (J.C.Reil 1800's) Autonomic nervous system replaced 'vegetative' nervous system by Langley 1898 maintain cardiovascular, gastrointestinal and thermal homeostasis and organization of stress responses the vegetative nervous system is composed of two antagonistic systems (H. Gaskell, 1886) sympathetic nervous system is a quick response mobilizing system parasympathetic as a more slowly activated system 3 Evening Seminar Notes-Physiology

4 TOPICS Nr The parasympathetic division of the autonomic nervous system. Characterize the structural organization of the parasympathethic nervous system: give the location of the cell bodies and axons of preganglionic neurons, also of the cell bodies and axons of ganglion cells. Classify the axons of the autonomic nervous system found in peripheral nerves according to the Erlanger- Gasser classification (B and C fibers). Characterize the synaptic connection between the preganglionic axon and the ganglion cell. Define the term autonomic ground plexus. Describe the structure and function of axon varicosities. Describe the biosynthesis, synaptic release, and elimination of acetyl-choline. Describe the effects of acetyl-choline of the receptors of target cells. Give examples of parasympathethic effects mediated by cholinergic receptors. Give further neurotransmitters released by parasympathetic nerves, and give examples of parasympathetic effects mediated by such neurotransmitters. Define the term autonomic tone. 11. The sympathetic division of the autonomic nervous system. The adrenal medulla. Characterize the structural organization of the sympathethic nervous system: give the location of the cell bodies and axons of preganglionic neurons, also of the cell bodies and axons of ganglion cells. The sympathetic adrenergic system: describe the biosynthesis of noradrenaline and adrenaline, the synaptic release and elimination of noradrenaline. List the adrenergic receptor types found on target cells along with the respective signal transduction pathways. Give examples of adrenergic effects mediated by each receptor type. Describe the anatomical structure of the adrenal medulla and the regulation of hormone release. Describe the transport of catecholamines in the circulation, their metabolism and excretion. Give examples of sympathetic cholinergic effects, and also of non-adrenergic non-cholinergic (NANC) 4 sympathetic effects. Evening Seminar Notes-Physiology 4

5 FUNCTION AUTONOMIC INNERVATION: Sympathetic and Parasympathetic Innervation of Effector Organs Dual-innervation mostly, excepting: adrenal medulla arrector pili muscles sweat glands most blood vessels lacrimal gland acini ciliary muscle musc. sphincter pupillae musc.dilatator pupillae - innervated by the sympathetic division only - by the parasympathetic division only Antagonistic effect mostly, excepting: innervation of salivary glands penile erection and 5 ejaculation (the two systems can work together to carry out physiological function) Evening Seminar Notes-Physiology 5

6 DUAL-ANTAGONIST INNERVATION II. Autonomic Innervation of Some Effector Organs 6 The autonomic innervation of the pupil and the salivary glands Evening (Clinical Seminar Neuroanatomy-Snell,1980) Notes-Physiology

7 EXEMPTION INNERVATION OF THE PUPIL 7 Evening Seminar Notes-Physiology

8 STRUCTURE STRUCTURAL ORGANZATION OF THE AUTONOMIC NERVE PATHWAY : TWO-NEURON CHAIN Ganglion: neuronal cell bodies in PNS Nuclei: neuronal cell bodies in CNS J N LANGLEY-The observation: Application of nicotine to the ganglion interrupted the transmission of nerve impulses from the preganglionic to the post-ganglionic nerve fibre => each ganglion represents a form of switching station Nicotine The one exception to the two-neuron pathway rule: Chromaffin cells of the adrenal medulla- the synapse is directly efferent onto the target cell bodies 8 Evening Seminar Notes-Physiology 8

9 STRUCTURE COMPARSION OF THE SYMPATHETIC AND PARASYMPATHETIC DIVISION: DIFFERENCES IN THE AUTONOMIC NERVE PATHWAY Location of the preganglionic neurons cell bodies CNS Classification of preganglionic axons: type B fiber Preganglinoic neurotransmitter: Ach (nach-receptor) Location of the ganglia (site of synapses) Classification of the postganglionic axons: type C fiber Postganglionic neurotransmitter Preganglionic fiber Postganglionic fiber Effector organ 9 Evening Seminar Notes-Physiology 9

10 DIVISION I. A. THE SYMPATHETIC PATHWAY Location of the preganglionic neurons cell bodies: Thoraco-lumbar (T1-L2/3) outflow from CNS; neurons located in the lateral horn of spinal cord Location of ganglia: a. Paravertebral: (Close to CNS= preganglionic fibers- short, postganglionic fibers- long) sympathetic trunk, 3 upper cervical ggl. b. Prevertebral: (located in the walls of major abdominal arteries) coeliac, superior mesenteric, inferior mesenteric ggl. c. Terminal ganglia- suprarenal medulla Postganglionic neurotransmitter: a. Noradrenaline [NA, Norepinephrine] b. Adrenaline [A, Epinephrine] 10 by adrenal medulla c. Sympathetic fibers of sweat glands- cholinergic (Ach) Evening Seminar Notes-Physiology 10

11 STRUCTURE THE SYMPATHETIC PATHWAYS Cranial Thoracic Lumbar Sacral 11 3 Lecture Outline Homeostasis Divisions of the ANS Cellular Organization of the ANS Pathways of the ANS Pharmacology of Autonomic Function Clinical. Published byjuniper Pope Evening Seminar Notes-Physiology 11

12 STRUCTURE THE SYMPATHETIC TRUNK: PARAVERTEBRAL CHAIN Sympathetic trunk: a vertical row on either side of the vertebral column that run from the base of the skull to the coccyx; interconnected paravertebral ganglia each preganglionic neuron synapses with many postganglionic neurons SUPERIOR CERVICAL GGL.. Sympathetic trunk MIDDLE CERVICAL GGL.. INFERIOR (STELLATUM) GGL. 12 Evening Seminar Notes-Physiology 12

13 DIVISION II. B. THE PARASYMPATHETIC PATHWAY Location of the preganglionic neurons cell bodies: Cranio-sacral outflow from CNS - four pairs parasympathetic nuclei in the brainstem (in connection with cranial nerves): EDINGER-WESTPHAL (n. III.), SUP.SALIVATORY (n. VII.) INF.SALIVATORY (n. IX.), DORSAL N. OF VAGUS (n. X.) - lateral horn of 2nd to 4th sacral segments of the spinal cord Location of ganglia: (Close to effectors) - four distinct parasympathetic ganglia in head: CILIARY ggl., PTERYGOPALATINE ggl., SUBMANDIBULAR ggl., OTIC ggl. connected with III., VII., and IX. n. - sacral outflow: termial ganglia (embedded in organ walls) Postganglionic neurotransmitter:acetylcholine 13 Evening Seminar Notes-Physiology 13

14 DIVISION II. B. THE CRANIAL PARASYMPATHETIC SYSTEM (III., VII., IX., X.) 14 Evening Seminar Notes-Physiology

15 AUTONOMIC NERVOUS SYSTEM STRUCTURE PARASYMPATHETIC PATHWAYS Eye Salivary Gland Cranial Bronchial tree Heart Liver Thoracic GI tract Adrenal medulla Lumbar Sacral 15 3 Lecture Outline Homeostasis Divisions of the ANS Cellular Organization of the ANS Pathways of the ANS Pharmacology of Autonomic Function Clinical. Published byjuniper Pope Urinary bladder Sex organs Evening Seminar Notes-Physiology 15

16 AUTONOMIC NERVOUS SYSTEM STRUCTURE LOCATION OF PARASYMPATHETIC GANGLIA 4 distinct ganglia in the head: n.iii.-ciliary ggl., n. VII.-pterygopalatine and submandibular ggl.s n.ix.- otic ggl. The remaining ganglia do not have specific names (n.x.) Sacral outflow: terminal ganglia embedded in organ walls 3 Lecture Outline Homeostasis Divisions of the ANS Cellular Organization of the ANS Pathways of the ANS Pharmacology of Autonomic Function Clinical. Published byjuniper Pope One preganglionic fiber makes synaptic connection with one-or two postganglionic neurons Evening Seminar Notes-Physiology 16

17 HOT TOPICS (Nr.10-11) Define the term autonomic ground plexus Describe the structure of axon varicosities Define the term autonomic tone Describe the biosynthesis of noradrenaline and adrenaline Synaptic release and elimination of noradrenaline List the adrenergic receptor types Give examples of adrenergic effects 17 Evening Seminar Notes-Physiology 17

18 HOT TOPICS (Nr.10-11) AUTONOMIC GROUND PLEXUS: The connection between the nervous system and the muscle the terminal regions of postganglionic neurones reaching the smooth muscles and forming a ground plexus Nerve plexus of sympathetic or parasympathetic axons, often containing autonomic neurons, ganglia and glial cells. 18 ((Falck, 1962) Network of varicose terminal axons containing norepinephrine in iris... A plexus of axons running in a finemeshed network of anastomosing strands formed by the terminal Schwann plasmodium. All the effector cells are probably in direct contact with this ground plexus. The Functional Organization of the Peripheral Autonomic Innervation by Hillarp (1949) Evening Seminar Notes-Physiology 18

19 HOT TOPICS (Nr.10-11) Common presynaptic arrangements: 1; terminal enlargements ( boutons )- neuronal synapses 2; terminal varicosities- autonomic neuroeffector synapses 3; terminal ramificationsneuromuscular synapses 3;; varicosity: A type of synapse in which the presynaptic cell releases neurotransmitter at a series of swellings along the axon 19 Evening Seminar Notes-Physiology 19

20 HOT TOPICS (Nr.10-11) Non-synaptic transmission and the structure of autonomic neuromuscular junction : AXON VARICOSITY in the vicinity of the effector tissue, terminal portions of Scanning electron micrographs: Resemble string of pearls autonomic nerve fibers become varicose (=enlarged) presynaptic cell releases neurotransmitter at a series of swellings along the axon; transmitters being released en passage from varying distances from the effector cells Varicosities occuring at 5-10 m intervals while there is no structural post-junctional specialization on effector cells, receptors for neurotransmitters accumulate on cell membranes at close junctions Uehara and Suyama (1978). J. Electron. Microsc. (Tokyo) 27, Burnstock (1988) Autonomic neural control mechanisms. With special reference to the airways. In: Kaliner, M.A., Barnes, P.J. (Eds.) muscle effectors are bundles rather than single smooth 20 muscle cells, that are connected by gap junctions Evening Seminar Notes-Physiology 20

21 HOT TOPICS (Nr.10-11) Define the term AUTONOMIC TONE Some sympathetic and parasympathetic neurons have a constant rate of firing under normal conditions known as AUTONOMIC TONE continuous background electrical activity results in continuous release of Ach or NA- exerting tonic influence on the function of the target organ (Phasic: momentary, burst spike firing- response to a sensory or pharmacological stimulus) vs. Tonic: sustsained, caused by spontaneously occurring baseline spike activity) Sympathetic Vasomotor tone: most blood vessels receive only sympathetic innervation keeps vasculatura and arterioles partially constricted and this maintains blood pressure-> loss of sympathetic tone: cause a rapid drop in blood pressure Parasympathetic Bronchomotor tone: vagal, cholinergic bronchospasm Sympathetic nerve discharge: SYMPATHETIC TONE Heesch, C M (1999)- Am J Phys holds resting heart rate (70-80 /min.) Arteriole diameter: -if the Vagus nerves to the heart are cut the heart 21 beats as its own intrinsic rate of ~100 /min. (denervated heart-transplantation) decreased sympath. baseline conditions increased sympath. activity =tonic sympath.act. activity Evening Seminar Notes-Physiology

22 HOT TOPICS (Nr.10-11) The sympathetic neuroeffector molecules: NORADRENALINE and ADRENALINE Preganglinoic neurotransmitter: Acetyl-choline (Ach) effect on nach-receptor Postganglionic neurotransmitter: Noradrenaline (NA) Adrenaline by adrenal medulla Sympathetic fibers of sweat glands are cholinergic Transmitter destruction: slow enzymatic digestion by COMT- postjunctional non-neuronal tissues and MAO- due to reuptake; prejunctional neuronal digestion Co-transmitters: ATP and NPY act on their own receptors on the effector tissue synergistic actions and/or pre- and post-junctional neuromodulation of neurotransmitter release 22 Cook and Burnstock (1976) two different vesicle types perhaps Evening representing Seminar Notes-Physiology cotransmitters 22

23 Adrenal medulla-chromaffin cells Adrenergic cells Dopaminergic cells THE AUTONOMIC NERVOUS SYSTEM HOT TOPICS (Nr.10-11) THE LIFE CYCLE OF NORADRENALINE: Synthesis, storage, release and elimination occurs in the nerve terminal Biosynthesis: Elimination: Tyrosine Tyrosine-hydroxylase L-DOPA DOPAMINE Dopamine--hydroxylase NORADRENALINE (Norepinephrine) ADRENALINE (Epinephrine) Phenylethanolamine-N-methyltransferase Release MAO, COMT - - inhibitors - MAO (mostly intraneuronally) COMT (membrane-boundpostsynaptically and soluble form-widely distributed) Adrenoceptors Neuronal uptake post-synaptically Tyrosine-hydroxylase: in the cytoplasm Dopamine -hydroxylase: in the storage vesicles 23 Catecholamine catabolism: catalyzed by either MAO and COMT Evening Seminar Notes-Physiology 23

24 HOT TOPICS (Nr.10-11) THE LIFE CYCLE OF NORADRENALINE: Synthesis, storage, release and elimination RESERPINE AND COCAINE BLOCKING OF THE UPTAKE AND STORAGE MECHANISMS IN ADRENERGIC NERVES. HILLARP NA, MALMFORS T.Life Sci.1964 Jul;3:703-8 STORAGE: Storage form- granular complex within vesicles in noredrenergic nerve terminals Reserpine (NA and) Dopmaine (DA) uptake into storage vesicles is reduced and the storage complex is disrupted => Depletion of NA Cocaine reuptake inhibitor of NA (monoamine transporter blocking) => increased level in the synaptic cleft Neuronal MonoAmine- Transporter Kokain - Szinaptikus vezikula RELEASE: Ca 2+ -dependent exocytosis Substances enhance release into the synaptic cleft (tyramine, ephedrine, ampethamine) 24 D,NA,A Vezikular MonoAmine- Transporter 24 Evening Seminar Notes-Physiology 24

25 HOT TOPICS (Nr.10-11) List the ADRENERGIC RECEPTOR TYPES Two main groups of adrenergic receptors: α and β G-protein coupled receptors G q -coupled, linked to phospholipase C IP3 Ca 2+ smooth muscle contraction G i coupled, linked to adenylate cyclase camp MLCK activation smooth muscle contraction Ca 2+ -channel inactivation release inhibition : G s -coupled, linked to adenylate cyclase camp (smooth muscle) inhibits MLCK smooth muscle relaxation (heart): PKA Ca 2+ -channels phosphorylatedca 2+ - entry increased contraction force in heart 25 Note: differential effects of increased camp in smooth muscle compared to cardiac muscle Evening {MLCK=myosin-light-chain-kinase} Seminar Notes-Physiology 25

26 HOT TOPICS (Nr.10-11) Give examples of ADRENERGIC EFFECTS Adrenaline is far more potent -adrenoceptor agonist than NA (drug-arrythmias) Substances e.g. caffeine, theobromine (cola) inhibit phosphodiesterase= prolong the life of camp prolong the effect of -adrenoceptor stimulation on vascular smooth muscle: Vasoconstriction increased peripheral resistance, increased blood pressure Mydriasis (dilation of the pupil) Closure of sphincter of the bladder : presynaptically: inhibit noradrenaline and acetylcholine release from presynaptic terminal 26 (inhibitory autoreceptor/ heteroreceptor) inhibit insulin release on pancreatic beta cells on the heart: Increases in contractile force (+-inotropic) Increases in heart rate (+chronotropic) (Presynaptic NA stimulation) on airway smooth muscle: Relaxation ( activation used to treat asthma) lipolysis in adipocytes (cardiovascular tissues?) Overactive Bladder and the β3-adrenoceptor Agonists: Current Strategy and Future Evening Prospects. Seminar Giarenis Notes-Physiology et al. Drugs

27 EFFECTS Cardiac muscle 27 Sympathetic Parasympathetic 1. Heart rate Increased Decreased 2. Force of vent. cont. Increased (Little effect) Smooth muscles Glands 1. Blood vessels Gen. constricted (Little effect) 2. Iris Pupils dilated (dilator m. constricts) Pupils constricted (constrictor m. constricts) 3. Bronchi Dilated (hormonal) Constricted 4. Gastrointestinal tract Inhibited (usu.) Stimulated (usu.) 5. Urinary bladder Inhibited Contracted 6. G.I. and Urin. Sphincters Contracted (usu.) Relaxed 7. Uterus Variable Variable 8. Pilomotor muscles Contracted - 1. Salivary glands Stim. (viscous) Stim. (watery) 2. Gastrointestinal glands Inhibited (usu.) Stimulated 3. Sweat glands Stimulated - Evening Seminar Notes-Physiology Adrenal medulla Stimulated -

28 Nicotine NICOTINE In response to the nicotine contained in a cigarette: Note: nicotine stimulates the postganglionic neurons of both the sympathetic and parasympathetic divisions! Heart rate may either increase or decrease Heart rhythm tends to become less regular (simultaneous actions on the sympathetic division, which increase the heart rate, and the parasympathetic division, which decreases the heart rate) Blood pressure tends to increase (because of the constriction of blood vessels, which are almost exclusively innervated by sympathetic neurons) motor activity of the bowel increased (stimulation of the parasympathetic ganglia) also affects the central nervous system Nicotine is extremely toxic- lethal dose: 500 and 1000 mg 28 Nicotine dosage in a traditional cigarette: 18 mg Evening Seminar Notes-Physiology 28

29 Clinical aspects Horner syndrome: interruption of sympathetic supply to head and neck Constiction of pupil (= Miosis) Dropping of upper eyelid (= Ptosis) Reduced prominence of the eyeball (= Enopthalmosis) Anhidrosis Bronchodilation: to inhibit cholinergic vasospasm a. Anticholinergic drug administration is more effective in patients with chronic bronchitis or emphysema (high cholinergic tone) b. Bronchial asthma: ß-agonist because of direct smooth muscle relaxation 29 Evening Seminar Notes-Physiology 29

30 Clinical aspects-medication Symphatic and Parasympathetic Effects -MYMETICUM and -LYTICUM Sympathomimetic agents: ß-agonist e.g. used to dilate bronchioles in respiratory disorders Sympatholytics: 1-blocker, -receptor antagonist used to treat high blood pressure Parasympathomimetic agents: activate muscarinic receptor; e.g. used to stimulate the urinary bladder following surgery; e.g. MUSCARINE Parasympatholytics: ATROPINE - bind to and block the action of muscarinic receptors dilate the pupil- eye examinations 30 Evening Seminar Notes-Physiology 30

31 Pharmacology Sympathetic and Parasympathetic Medication 31 Evening Seminar Notes-Physiology

32 A Case Description of a case: Patient: a 48-year-old women Complaint: 1.Racing heart 2.Cold hands and feet 3.Feeling hot 4.Headaches 5.Nausea, vomiting Medical check-up: 6. Extremely elevated blood pressure (235/125) 7. Urine sample-eleveted levels of metanephrine, 8. CT-mass on her adrenal medulla 32 from Costanzo, Physiology 5th edition (2014) Elsevier Evening Seminar Notes-Physiology

33 A Case Description of a case: from Costanzo, Physiology 5th edition (2014) Elsevier Patient: a 48-year-old woman Complaints: Explanation of case: 1.Racing heart 1.Increased heat rate and contractility 1 2.Cold hands and feet 2.Vasoconstriction in skin vascular smooth muscles 1 3.Feeling hot 3.Impaired ability to dissipate heat because of vasoconstr. in skin 4.Headaches 4.Secondary to elevated blood pressure 5.Nausea, vomiting 5.Due to effects on gastrointestinal smooth muscles Medical check-up: 6. Extremely elevated blood pressure (235/125) 6. Increased vasoconstriction+heart effects 7. Urine sample-eleveted levels of metanephrine, 7. Metabolic products of cathecholamines 8. CT-mass on her adrenal medulla Diagnosis: Pheochromocytoma-tumor of chromaffin cells Treatment: A combination of 1 (e.g. prazosin) and 1 33 antagonists (propranolol) until surgery In contrast to normal adrenal medulla, which secretes mainly adrenaline, pheocromocytomas secrete mainly NA Evening Seminar Notes-Physiology