Autonomic Nervous System Lecture Notes PDF

Autonomic Nervous System Dr Vassilis Beglopoulos Slides by Dr Philip Welsby 1 Lecture Content - 1 hour st  Introduction to the autonomic NS  ANS controls visceral organs  Neurotransmitters...

Autonomic Nervous System Dr Vassilis Beglopoulos Slides by Dr Philip Welsby 1 Lecture Content - 1 hour st  Introduction to the autonomic NS  ANS controls visceral organs  Neurotransmitters are acetylcholine and noradrenaline SUGGESTED READING  Rang et al., Rang and Dales Pharmacology, 8th ed., Parts of Chapters 4, 12, 13 & 14  Silverthorn, Human Physiology: An Integrated Approach, 7 th ed., Parts of Chapters 5, 8 & 11 2 Somatic Nervous System Afferent and Efferent divisions 3 Overview of the Nervous System 4 http://www.ninds.nih.gov/disorders/brain_basics/ninds_neuron.htm  Autonomic Nervous System (ANS)  The ANS consists of motor neurons that: 1. Innervate smooth muscle, cardiac muscle, internal organs & skin 2. Makes adjustments to ensure optimal support for body activities 3. Operate via subconscious control 4. Have viscera as most of their effectors 5 ANS vs. SNS Efferent Pathways  SNS: ◦ Heavily myelinated axons of the somatic motor neurons extend from the CNS to the effector  ANS: ◦ Axons of the ANS are a two-neuron chain  Preganglionic (first) neuron has a lightly myelinated axon  Ganglionic (second) neuron extends to an effector organ 6  ANS vs. SNS Neurotransmitters  SNS: ◦ All somatic motor neurons release ACh  Has an excitatory effect  ANS: ◦ Preganglionic fibres release ACh ◦ Postganglionic fibres release noradrenaline or ACh  Effect is either stimulatory or inhibitory  Effect is dependent upon the neurotransmitter released and the receptor type 7 Overview of the Autonomic Nervous System 8 ANS vs. SNS 9 Interaction of ANS Divisions  Most visceral organs are innervated by both sympathetic and parasympathetic fibres ◦ Results in dynamic antagonisms that precisely control visceral activity  Physiological antagonism!  Example: ◦ Sympathetic fibres:  Increase heart and respiratory rates, and inhibit digestion and elimination ◦ Parasympathetic fibres:  Decrease heart and respiratory rates, allow for digestion and discarding of wastes 10 Interaction of ANS Divisions  Cooperative effect: ◦ ANS cooperation is best seen in control of the external genitalia  Parasympathetic fibres cause vasodilation and are responsible for erection of the penis and clitoris  Sympathetic fibres cause ejaculation of semen in males and reflex peristalsis in females 11 Sympathetic: Parasympathet thoracolumba ic: craniosacral r 12 Parasympathetic Division  Concerned with keeping body energy use low ◦ Involves the D activities – digestion, defecation, and diuresis ◦ “Rest & Digest”  Its activity is illustrated in a person who relaxes after a meal 1. Blood pressure, heart rate, and respiratory rates are low 2. Gastrointestinal tract activity is high 3. Pupils are constricted  Largely innervates the internal organs – not the skin  Neurotransmitter: ◦ Acetylcholine at both ganglionic and effector organs 13 Parasympathetic Division  Vagal nerve ◦ Visceral organs of thorax & abdomen:  Stimulates digestive glands  Increases motility of smooth muscle of digestive tract  Decreases heart rate  Causes bronchial constriction 14 Sympathetic Division  Concerned with high energy use ◦ Involves the E activities – exercise, excitement, emergency, and embarrassment ◦ “Fight-or-flight”  Promotes adjustments during exercise ◦ Blood flow to organs is reduced, flow to muscles is increased  Its activity is illustrated by a person who is threatened 1. Heart rate increases, and breathing is rapid and deep 2. Skin is cold and sweaty, and the pupils dilate  Innervates every part of the body  Neurotransmitters: ◦ Ganglionic is acetylcholine ◦ Effector organ neurotransmitter is noradrenaline (i.e. adrenergic) 15 Sympathetic Division 16 Sympathetic Division Adrenal Gland  Adrenal gland sits on top of the kidneys ◦ Major part of the sympathetic nervous system ◦ Activation causes systemic release of adrenaline 17 Peripheral Receptors - at Target Tissue  Cholinergic Receptors ◦ Receptors that mediate responses to acetylcholine  Muscarinic  Adrenergic Receptors ◦ Receptors that mediate responses to adrenaline and noradrenaline  Alpha (a) & Beta (b) adrenergic 18  ANS Peripheral Receptors  Parasympathetic  Sympathetic 19 ANS Agonists and Antagonists 20 Summary - 1 hour st  PNS includes the somatic and autonomic NS  SNS controls skeletal muscle ◦ Neurotransmitter is ACh  ANS controls visceral organs ◦ Neurotransmitters are ACh and noradrenaline and adrenaline 21 Lecture Content - 2 nd hour  Introduction to sympathetic synapses ◦ Neurotransmitters and drugs targeting it  Introduction to parasympathetic synapses ◦ Neurotransmitters and drugs targeting it SUGGESTED READING  Rang et al., Rang and Dales Pharmacology, 8th ed., Parts of Chapters 4, 12, 13 & 14  Silverthorn, Human Physiology: An Integrated Approach, 7th ed., Parts of Chapters 5, 8 & 11 22 Quick quiz Central Nervous System ________ ______ _____ (CNS) Peripheral Nervous System _____ ______ (CNS) _____ ______ _____ ______ _____ ______ ___ ____ ___ ___ ____ ___ ______ _____ ________ ________ ____ ____ 23 24 Overview of the Autonomic Nervous System 25 Peripheral Receptors at Target Tissue  Cholinergic Receptors ◦ Receptors that mediate responses to acetylcholine  Muscarinic  Adrenergic Receptors ◦ Receptors that mediate responses to adrenaline and noradrenaline  Alpha (a) & Beta (b) adrenergic 26 Sympathetic Nervous System Adrenergic Receptors Noradrenaline and adrenaline bind to two adrenergic receptors ◦ Alpha and beta  a1 + a2  b1 + b2 (b3) 27 http://courses.washington.edu/chat543/cvans/sfp/ansr G-protein-coupled receptors Signal Transduction Mechanism Receptor activated G protein – A family of proteins that bind GTP G Protein-GDP + GTP G Protein-GTP + GDP Inactive Active receptor receptor G-protein-coupled receptors 30 Bear et al., Neuroscience Exploring the Brain, 3 rd ed  Sympathetic Nervous System a-Adrenergic Receptors  a1 ◦ Ocular: mydriasis ◦ Blood vessels: vasoconstriction ◦ Male genitals: ejaculation ◦ Bladder neck and prostate: contraction  a2 ◦ Located on presynaptic terminal ◦ Inhibits release of norepinephrine ◦ Located in PNS and CNS 31  Sympathetic Nervous System b-Adrenergic Receptors  b1 ◦ Heart: Increased output  b2 ◦ Bronchi: dilation ◦ Uterus: relaxation of uterine smooth muscle ◦ Arterioles in heart, lungs, skeletal muscle: vasodilation ◦ Glycogenolysis 32 Sympathetic Nervous System Adrenaline 1. Synthesized in adrenal medulla ◦ Noradrenalin converted to adrenalin 2. Stored in vesicles in adrenal medulla 3. Released into bloodstream after AP ◦ Travels in blood throughout the body ◦ Metabolized by the liver 33 http://en.wikipedia.org/wiki/Epineph Sympathetic Nervous System Noradrenergic Synapses  Noradrenaline 1. Synthesized in presynaptic terminal from precursors & stored in vesicles 2. Released after action potential 3. Binds to receptors  a2 on the presynaptic neuron  a1 or b1 on postsynaptic cell 4. Reuptake by presynaptic neuron  Reused or broken down by MAO (monamine oxidase) 34 Sympathetic Nervous System Noradrenergic Synapses 35 Sympathetic Nervous System Sympathomimetics  Salbutamol - b2 agonist (bronchodilation) ◦ Use - bronchospasm, asthma, bronchitis ◦ Side effects - nervousness, restlessness ◦ Contraindicated - severe cardiac disease, hypertension  Epinephrine/Adrenaline - stimulates a & b ◦ Use - allergic reaction, cardiac arrest ◦ Side effects - nervousness, agitation ◦ Contraindicated - cardiac dysrhythmias 36 http://www.saigon-gpdaily.com.vn/Health/2012/4/10 Sympathetic Nervous System b-Blockers  Propranolol ◦ Non-selective b-antagonist ◦ Indications:  Angina, hypertension, cardiac dysrhythmias, anxiety ◦ Side effects – bronchoconstriction, fatigue, depression, hypoglycaemia ◦ Contraindicated – asthma, heart block  Metoprolol ◦ b1 (cardio) selective antagonist ◦ Indications:  Mild to moderate hypertension, angina, dysrhythmias 37 http://www.cvpharmacology.com/cardioinhibitory/beta-blockers. Parasympathetic NS  Autonomic tone: ◦ Steady day-to-day influence exerted by the autonomic system ◦ Usually only one division provide tone  Parasympathetic system usually provides the basal tone 38 Parasympathetic Nervous System Cholinergic Receptors  Nicotinic: ◦ Promotes ganglionic transmission at all ganglia  Muscarinic: ◦ Increased gland secretion ◦ Contraction of smooth muscle (bronchi, bladder, GI) ◦ Slow heart rate ◦ Contraction of iris (miosis) and ciliary (focus) 39 Cholinergic Synapses 1. Acetylcholine is synthesized in presynaptic terminal from choline and Acetylcoenzyme A 2. Stored in vesicles and released with action potentials 3. Binds to receptors on postsynaptic cell ◦ Dissociates ◦ Broken down by acetylcholinesterase on post-synaptic cell membrane  Acetate & choline ◦ Choline is re-absorbed by neuron to synthesize more ACh 40 Cholinergic Synapses 41 Parasympathetic Nervous System Cholinergic Agonists  Agonists for muscarinic receptors ◦ Mimic action of acetylcholine ◦ Do not activate nicotinic receptors ◦ Pilocarpine - glaucoma  Topical application – activates M3 receptors  Muscle contraction & miosis http://www.vision-and-eye-health.com/glaucoma-surgery.html 42 http://www.umm.edu/patiented/articles/what_glaucoma_000025_ Parasympathetic Nervous System Cholinergic Antagonists  Atropine: ◦ Non selective competitive muscarinic receptor antagonist  Inhibits ACh binding - blocks vagal effects on certain nodes - increases conduction & heart rate ◦ Use:  Adjunct for anaesthesia – reduces secretions and causes bronchodilation  Anti-cholinesterase inhibitor poisoning ◦ Side effects:  Most frequent = dry mouth, blurred vision, urinary retention, constipation 43 http://www.cvpharmacology.com/antiarrhy/atropin