Autonomic Nervous System Fight Or Flight Vs. Rest And Digest

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1 Autonomic Nervous System Fight Or Flight Vs. Rest And Digest Prof. Dr. Farooq Ahmed Director Medical Education Khyber Medical College

2 Learning objectives At the end of these 2 presentations, the students of 2 nd year will be able to; 1) Describe the basic physiologic anatomy of ANS 2) Discuss the different receptors and neurotransmitter related to ANS 3) Discuss the physiological effects of ANS on different organs and systems 4) Apply the basic knowledge of physiology of ANS in different clinical settings

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5 Physiologic anatomy of ANS Contents Autonomic Nuclei in the brain and spinal cord Afferent limb of ANS Efferent limb Ganglia Sympathetic NS Parasympathetic NS Sympathetic Parasympathetic Organs supplied by sympathetic NS Organs supplied by parasympathetic NS Role of adrenal medulla Receptors Sympathetic Parasympathetic Neurotransmitters Epinephrine/Norepinephrine Acetylcholine Clinical and therapeutic implications Summary Questions

6 Introduction Part of involuntary control mechanisms of the body Has 2 parts; Sympathetic / parasympathetic Regulating centers in the brain Adrenal medulla is part of sympathetic NS Different type of receptors involved Receptors act through different neurotransmitters, mainly ACh. and Norepinephrine

7 Reflex arc Afferent fibers Efferent fibers

8 N Cerebral cortex Limbic lobe Hypothalamus Reticular formation Spinal cord

9 Afferent inputs of ANS Arteries Baroreceptors Gut Heart Pulmonary receptors Chemoreceptors Brain- cerebral cortex / limbic system

10 Efferent limb of ANS Presynaptic neurons Myelinated Cholinergic Long in case of PNS, while short in SNS Ganglia Postsynaptic neurons Non-Myelinated Adrenergic (SNS), Cholinergic (PNS) Long in case of SNS, while short in PNS

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12 Autonomic ganglia Sympathetic ganglia Parasympath etic ganglia

13 Ganglia of sympathetic NS Near the spinal cord Preganglionic fibers run in antero-mediolateral column of spinal cord Ganglia lie on each side of vertebral columns Arises from T1-L2 spinal segments

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16 Ganglia of parasympathetic NS Cranial (3 rd, 7 th, 9 th, 10 th cranial nerves) Extramural ganglia Sacral (S2-4) Intramural ganglia

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18 Physiological actions of SNS

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20 Organs supplied by SNS Organs supplied Physiologic actions upon stimulation Ciliary muscles of the eyes Dilatation of pupils Heart Lungs Arteries and veins GIT Adrenal medulla Uterus Urinary bladder External genitalia Skin, sweat glands, erector pili Salivary glands Adipose tissues +ionotrophy + chronotrophy Bronchodilatation Vasoconstriction Organ relaxation, sphincter constriction Release of catacholamines Uterine relaxation Wall relaxation, trigon contraction Ejaculation Sweating?, piloerection Salivation (Cholinergic) +BMR, lipolysis

21 Physiological actions of PNS

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23 Organs supplied Physiologic actions upon stimulation Ciliary muscles Pupilary constriction Salivary glands Secretion Heart - Inotropic and - chronotropic GIT Viscous contractions, sphincter dilatation Urinary bladder Wall contraction, trigon dilatation External genitalia Erection

24 Role of Adrenal Medulla in SNS

25 Adrenal Medullary Hormones 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% epinephrine norepinephrine

26 Biosynthesis

27 Receptors of ANS Sympathetic Parasympathetic

28 Receptors of SNS Alpha adrenergic receptors α1 α2 Beta adrenergic receptors β1 β2 β3

29 Distribution of adrenergic receptors Receptor type Organs Physiologic effects upon stimulation α1 adrenergic receptors α2 adrenergic receptors β1 adrenergic receptors β2 adrenergic receptors CNS (Hippocampus, cortex) Blood vessels Heart Liver Vas deferens CNS (locus ceruleus) Blood vessels Fats Iris Carpus striatum Heart Adipose tissues Blood vessels Uterus Bronchial smooth muscles Excitation Vasoconstriction +inotropic effect Glycogen phosphorylation Contraction of vas deferens Inhibition Vasoconstriction Inhibition of lipolysis Pupillary dilatation +inotropic and chronotropic Vasodilatation Inhibition of contractions Bronchodilatation β3 adrenergic receptors Adipose tissues thermogenesis

30 Cholinergic Receptors of PNS Muscarinic receptors Nicotinic receptors

31 Distribution of Cholinergic receptors Receptor type Distribution Effects upon stimulation Muscarinic receptors (M1 / M2) Sweat glands Blood vessels (in skeletal muscles) Parasympathetic effector organs Ganglia Hippocampus, cortex thalamus Sweating Vasodilatation Nicotinic receptors Skeletal muscle end plate Neuromuscular junctions Smooth muscles Contraction of skeletal and smooth muscles

32 Neurotransmitters in ANS Acetylcholine Norepinephrine / Epinephrine

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36 Inactivation of neurotransmitters at synaptic clefts Acetylcholine is inactivated by the enzyme ACETYLCHOLINESTERASE (AChE)

37 Norepinephrine degradation Reuptake into: Presynaptic vesicles (MAO in Mitochondria) Metabolism by COMT mainly in liver

38 Summary of physiological actions of ANS on different organs McCorry, L. K. (2007). Physiology of the Autonomic Nervous System. American Journal of Pharmaceutical Education, 71(4), 78.

39 Organs SNS effects Receptors PNS effects Eye Pupillary dilatation Far vision α1 β2 Pupillary constriction Near vision Heart Blood vessels Lungs Heart rate Force of contraction Conduction velocity Constriction *weak constriction of skeletal blood vessels Airway dilatation Glandular secretion β1, β2 Heart rate Α1 β2 β2 α1, β Bronchoconstriction glandular secretion Erector pili Contraction Sweating Α1 Muscarinic Adrenal medulla Epinephrine, norepinephrine secretion Nicotinic --- Salivary glands Small volume α1, β2 Large volume

40 Organs SNS effects Receptors PNS effects Stomach Motility Sphincters Secretions intestines Motility Sphincters Secretions Decrease Contract Decrease Decrease Contract Decrease α1, β2 Increase Relax increase α1, β2 Increase Relax increase Gall bladder Relaxation β2 Contraction Pancreas Exocrine Endocrine Enzyme secretion Insulin secretion α α enzyme secretion Insulin secretion Urinary bladder Detruser Sphincter Relaxation Contraction β2 Contraction Relaxation Liver Adipose tissues Gluconeogenesis Glycogenolysis Lipolysis Αα1, β2 β

41 Summary of ANS control of different body functions

42 Body function SNS effects PNS effects Blood pressure Increase Decrease Heart rate Increase Decrease Bronchodilatation Dilatation Constriction GI motility and secretions Decrease Increase Sweating Increase Decrease Bladder functions Urination Inhibition Uterine contractions Dilatation --- Pupillary dilatation and constriction Dilatation Constriction

43 Clinical implications

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45 Adrenergic stimulant / blocking drugs

46 Drugs Site of action Clinical use α1 Adrenergic agonists: Epinephrine, ephedrine, dopamine, nephazoline, ozymetazoline Alpha / beta adrenergic receptors Selective Non-selective As vasoconstrictors In shock α2 Adrenergic antagonists: Prazocin, terazocin Alfuzocin Alpha-1 receptor blocker on blood vessels and prostate gland Hypertension Benign prostatic hyperplasia Others β2 agonists: Albuterol, terbutaline β2 receptors in bronchial tree Treatment of Bronchial Asthma β1 blockers: Atenolol, Bisoprolol β1- receptors in myocardium Angina, and other ischemic heart diseases

47 Cholinergic stimulant / blocking drugs

48 Drugs Site of action Clinical use Carbachol Pilocarpine Pyridostigmine Muscarinic receptors in smooth muscles of the eyes Anticholinesterase (indirect acting pro-cholinergic) Inducing miosis Glaucoma Myesthenia gravis Atropine Antagonist to muscarinic receptors Bradycardia, heart blocks Trimetaphan Ganglion blockers Malignant hypertension

49 Summary Sympathetic NS Parasympathetic NS Autonomic NS

50 T1-L2 Spinal segments Preganglionic neurons shorter than postganglionic neurons Preganglionic neurons are cholinergic Postganglionic neurons are adrenergic except to sweat glands and adrenal medulla Supplies most smooth muscles and cardiac muscles Physiologic action depends upon the receptor stimulated

51 Adrenergic receptors are: Alpha 1,2,3 Beta 1,2,3 Alpha receptors are present in blood vessels and bladder and other sites Beta receptors are present in heart, bronchi and other sites

52 Parasympathetic NS has cranio-sacral distribution Cranial N: 3,7,9,10 S2-4 spinal segments Both preganglionic and postganglionic neurons are cholinergic Muscarinic Nicotinic Supplies the heart, bronchi, gut, bladder, and external genitalia

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54 Question-1 Regarding the sympathetic division of the autonomic nervous system. a) Acetylcholine is secreted by some sympathetic postganglionic fibres. b) Most sympathetic preganglionic fibres secrete noradenaline (norepinephrine). c) Sympathetic postganglionic neurons are found in spinal segments from T1 to L2. d) The sympathetic chain extends from the thoracic to the sacral regions of the spinal cord.

55 Question-2 Regarding the parasympathetic division of the autonomic nervous system. a) Parasympathetic preganglionic fibres are found in all cranial nerves b) Parasympathetic vasoconstrictor fibres are present in the salivary glands. c) Parasympathetic postganglionic neurons are found in spinal ganglia from T1 to L2. d) Parasympathetic postganglionic fibres secrete acetylcholine onto their target organs.

56 Question-3 Which of the following statements regarding the role of the autonomic innervation are correct? Please select all that apply a) Stimulation of the sympathetic nerves to the eyes causes dilation of the pupils. b) Activation of the sympathetic system causes vasodilatation in the skin. c) Activation of the sympathetic system causes vasoconstriction in the viscera and vasodilatation in skeletal muscle. d) Stimulation of the vagus nerves speed up the heart

57 Question-4 Regarding synaptic transmission in the autonomic nervous system a) The acetylcholine receptors in both parasympathetic and sympathetic ganglia are predominantly muscarinic. b) Noradrenaline (norepinephrine) secreted by sympathetic postganglionic fibres acts preferentially on β-adrenoceptors. c) The adrenal medulla secretes adrenaline in response to activation of muscarinic sympathetic postganglionic fibres in the splanchnic nerves. d) Acetylcholine secreted by parasympathetic postganglionic fibres acts on muscarinic receptors.

58 Question-5

59 Question-6 true/false

60 Question-7 A Physician was discussing autonomic pharmacology with house officers. He asked when given to man, a drug causes bradycardia, increased GI motility and pupilary constriction. Which one of the following drug produces these combined effects: (a) Epinephrine (b) Acetylcholine like drug (c) Atropine (d) nor-epinephrine like drug

61 Question-8 A 35 years old patient was admitted in emergency dept. of a tertiary care hospital at 11 pm. He had severe breathlessness and had history of asthmatic attacks in the past. A Junior doctor was on duty, who nebulized him with SALBUTAMOL. This drug: (a)is a beta-2 agonist (b) Has its actions competitively antagonized by a anti-cholinergic drug (c) Produces constriction of blood vessels in skeletal muscles (d) Produces pupillary dilatation

62 Question-9 25 years old male patient was admitted in Hospital at 4pm, due to hypersensitivity reaction to some drug ingestion 4 hours before. At emergency he was treated by a drug which caused dilatation of vessels in muscle, constriction of cutaneous vessels, and positive inotropic and chronotropic effects on the heart. The drug given may be: (a) Adrenaline (b) Prazocin (alpha blocker) (c) Cholinergic drug- (pyridostigmine) (d) Terbutalin (B-2 agonist) (e) Ganglion blocker trimetaphan

63 Question-10 A 60 years old asthmatic man comes in for a check up and complains of having some difficulty in starting to urinate. Physical examination indicates that the man has a blood pressure of 160/100 mm of Hg and slightly enlarge prostate. Which of the following medications would be useful in treating both of these conditions: (a) Alpha blockers (b) beta-1 receptor blockers (c) Anticholinergic drugs (d) beta-2 receptor agonists (e) alpha-adrenergic receptor agonists

64 Did you achieve these Learning objectives 1) Describe the basic physiologic anatomy of ANS 2) Discuss the different receptors and neurotransmitter related to ANS 3) Discuss the physiological effects of ANS on different organs and systems 4) Apply the basic knowledge of physiology of ANS in different clinical settings

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66 Wish you best of luck for your future

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