Autonomic Nervious System Physiology_202324_MUB.pptx

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Autonomic Nervous System Biology Class Course Lecturer Date DEM Year 1 The Body: Movement and Function (BMF) Dr. Ebrahim Rajab ([email protected]) 12/11/2023 Learning objectives  Recall the divisions of the nervous syst...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Autonomic Nervous System Biology Class Course Lecturer Date DEM Year 1 The Body: Movement and Function (BMF) Dr. Ebrahim Rajab ([email protected]) 12/11/2023 Learning objectives  Recall the divisions of the nervous system  Contrast the anatomical features of the sympathetic and parasympathetic systems  Identify the functions of the sympathetic system (“fight-orflight”) Divisions of Nervous system Divisions of Peripheral Nervous System Divisions of Autonomic NS • The ANS is “involuntary” and maintains homeostatic conditions within the body • The ANS regulates the function of internal/visceral organs ( heart and circulation, digestive and respiratory system) in a coordinate manner • The ANS has two divisions* the parasympathetic and sympathetic; most visceral organs innervated by both divisions “dual innervation” • Two divisions exert (mostly) opposing effects • Partial activation under most circumstances: “tonic“ activity • *Technically, the enteric nervous system is a 3rd The autonomic nervous system uses division: vast network of nerve fibers different neurotransmitters to that innervate Internal organs/viscera controlled by ANS • Heart • Lungs • Stomach & GIT, spleen, pancreas • Bladder & rectum • Kidney & liver • Eye (pupil) A muscle or gland innervated by autonomic fibers is called an effector organ. If the autonomic nerve fibers to an effector organ are cut, the orga may continue to function, but will lack the capability of adjusting t Control of the ANS CNS has central control of ANS output – Medulla and Pons in brain stem • Centres controlling cardiovascular, respiratory & digestive systems. – Hypothalamus has major role (> HPA) • Heart rate, B.P. respiration (via medulla) – Spinal cord • Integrates autonomic reflexes not subject to higher control • e.g. urination, defecation Overview of the roles of the Sympathetic and parasympathetic NS Parasympathetic function Sympathetic function – Activated in non-emergencies – Activated in emergency situation – Promotes normal Restorative/maintenance of the body or when stress involved (sudden burst of energy required) – „Fight or Flight“ – Increases cardiac output and pulmonary ventilation, routes blood to muscles, raises blood glucose and slows down digestion, kidney filtration and other functions not needed during emergencies – Whole sympathetic system tends to "go off" together – „Rest & Digest“ – allows us to unwind and conserve energy – Promotes secretions and mobility of different parts of the digestive tract – Also involved in urination, defecation – Parasympathetic does not tend to “go off together” Advantages of dual ANS innervation • Most visceral organs are innervated by both sympathetic and parasympathetic nerve fibres - (so called “dual innervation”) which generally exert opposite effects in a particular organ • These features allow for rapid and precise control over organ/tissue‘s, and rapid transitions from rest state to ‘fight or flight’ • Example: Sympathetic stimulation increases heart rate whereas parasympathetic stimulation decreases it • Usually both systems are partially active, due to some level of basal Advantages of Dual ANS Innervation • The two divisions of the ANS are usually reciprocally controlled; increased activity in one division is accompanied by a corresponding decrease in the other • There are several exceptions to this general rule of dual reciprocal innervation by the two branches of the autonomic nervous system: – Blood vessels, e.g. arterioles and veins (sympathetic); – sweat glands (mainly sympathetic, release ACh not NA) – liver (glycogen released through SNS) Arrangement of SNS & PSNS pathways rasympathetic • Each eganglionic fibres are long and myelinated stganglionic nerves are short and unmyelinated • Parasympathetic Cranial Sacral Preganglionic fibre Postganglionic fibre Effector organ ganglion • Preganglionic fibre CNS pathway from CNS to organ/effector is two-neuron chain Sympathetic Thoracic Lumbar ANS Postganglionic fibre Effector organ • CNS → preganglionic ympathetic nerve → reganglionic fibres are short and myelinated ostganglionic nerves are long and unmyelinated ganglion → ganglion Modified Sympathetic Nervous System – Adrenal Medulla • Some preganglionic sympathetic fibers directly innervate the secretory cells of the adrenal medulla • Though the adrenal medulla is an endocrine gland, it is considered a modified sympathetic ganglion and is controlled by the sympathetic preganglionic fibres located in CNS • The cells of this gland are modified nerve cells, which do not give rise to axons, but release their transmitter (adrenaline 80% / NA 20%) Origins of the Parasympathetic Division “Craniosacral outflow” • Preganglionic neurons originate from the cranial nerves (III, VII, IX and X) and sacral spinal nerves (S2-S4). • Vagus nerve (X) carries nearly 80% of the total craniosacral flow. • Long myelinated preganglionic neuron • Ganglion lies close to the target organ • Short unmyelinated postganglionic neuron Sympathetic Nervous System Thoracolumbar outflow – Preganglionic: thoracic and lumbar regions of spinal cord (T1 – L3) – Sympathetic preganglionic nerves are short and myelinated) – Sympathetic postganglionic nerves are long (and unmyelinated) – Sympathetic ganglia lie in a chain along either side of spinal cord – sympathetic ANS Neurotransmitters and Receptors • Both sympathetic and parasympathetic preganglionic neurons release Acetylcholine (ACh) • Most postganglionic sympathetic neurons release noradrenaline (=norepinepthrine) • Most postganglionic parasympathetic neurons release ACh • Each autonomic neurotransmitter stimulates activity in some tissues but not in others. The type of activity or response depends on presence of a receptor on the tissue: – Adrenal medulla • Extension of sympathetic nervous system • Two adrenal glands: „Ad“ „renal“ - next to kidney • Outer adrenal cortex, inner adrenal medulla – Medulla is modified sympathetic ganglion w/out postganglionic fibres – Preganglionic fibre directly stimulates hormone release from chromaffin cells into the blood: 20% noradrenaline, 80% adrenaline Additional complexity and exceptions to the rules • Salivary gland secretion increased via both sympathetic and parasympathetic input • Blood vessels • Resistance vessels (Arteriolea) innervated by sympathetic NS only • Sweat glands • Mainly sympathetic innervation and terminal fibre release ACh(!) not NA(!) Neurotransmitter (NT) receptors of the ANS • Each autonomic NT can stimulate activity in some tissues but have lower activity in others – e.g. NA accelerates heart rate but decreases contraction of digestive tract • Response is “property” of the tissue, not the NT • Tissue/organ targets posses one or more receptor: binding of NT induces tissue-specific response • Note that receptors can be ionotropic or metabotropic. • Ionotropic: typically, ligand-gated ion channels, through which ions pass in response to a neurotransmitter, • metabotropic receptors require G proteins and second messengers to indirectly modulate ionic activity in neurons. NT receptor coupling 1 Ionotropic receptor 2 + Metabotropic receptor (G-protein coupled) + ++ ++ + + + + - - - b a g + - + + + + + + Postsynaptic cell cyclic AMP system Ca2+ second messenger system Cholinergic Receptors: nicotinic vs muscarinic Nicotinic type:  Found on all postganglionic ANS cell bodies  Receptor activated by ACh released from preganglionic parasymp. or symp. nerves  Receptor activated by tobacco derivative nicotine  Ionotropic, thus fast response  *NN or N2 – the NM or N1 is at the Cholinergic Receptors: nicotinic vs muscarinic Muscarinic type: • Binds ACh released from postganglionic parasympathetic nerves • Found on effector cell membranes – e.g. smooth muscle, glands, cardiac muscle • Receptor activated by mushroom poison muscarine • 5 types of muscarinic ACh receptor – All G protein-coupled metabotropic receptors Nicotinic Receptors – ACh binding opens Pre-ganglionic fibre intrinsic Na+/K+ channel • Nicotinic ACh receptor is ionotropic – Resulting in depolarisation of postsynaptic cell – Response is rapid – New action potential transmitted ACh ANS ganglion Na+ Nicotinic receptor ++ ++ Post-ganglionic fibre Muscarinic Receptors • M2 type: inhibitory response • Located on cardiac tissue • Receptor couples to increase K+ conductance, inhibit calcium channels • e.g. decrease heart contraction • M3 type excitatory response • Located in digestive system • G protein couples to Ca2+ second-messenger system • e.g. Increase glandular secretions, increase GIT motility NT receptors: Parasympathetic division Muscarinic receptor Effector tissue/organ ACh Na+ Parasympathetic ganglion Nicotinic receptor ++ ++ Post-ganglionic fibre e.g. cAMP e.g. PKA Cell response e.g. reduced heart rate Adrenergic Receptors types • • • • Only found at effector organ synapses Postsynaptically, after postganglionic sympathetic nerves Two major classes that bind noradrenaline and adrenaline All of these types couple to G proteins but intracellular coupling differs Adrenergi c a-adrenergic a1 a2 b-adrenergic b1 b2 b3 Adrenergic receptors a1: excitatory response • Located on most sympathetic target cells • G protein couples to Ca2+ second-messenger system • e.g. Increase contraction of arterioles → raised blood pressure a2: inhibitory response • Located in digestive system • G protein couples to inhibit cyclic AMP system • e.g. decreased smooth muscle contraction → reduced GIT motility Adrenergic receptors (IV) b1: excitatory response • Located in heart • Couples via G protein to cyclic AMP/PKA • e.g. contraction of cardiac muscle → increased rate & force b2: inhibitory response • Skeletal muscle (AD in blood), smooth muscle of some vessels & organs • Couples via G protein to cyclic AMP/PKA • e.g. relaxation of smooth muscle → bronchiolar dilation Effector organs/tissues express receptors for the NT of both types of postganglionic fibres: Postganglionic parasympathetic nerve ACh Postganglionic sympathetic nerve Synapse 1 Synapse 2 musAChR NA NA-R reduced contraction increased contraction Cardiac muscle Termination of NT effects • Acetylcholine – Destroyed by acetylcholinesterase at synpases • Noradrenaline – Re-uptake by pre- and post-synaptic cell then metabolized/re-cycled Termination of NT effects ACh destroyed by acetylcholinesterase (AChE) at synapse ACh receptors AChE Termination of NT effects NA is re-uptaken by pre- and postsynaptic cells then metabolized/recycled NA receptors STEPS OF NEUROCHEMICAL TRANSMISSION = POTENTIAL TARGETS FOR PHARMACOLOGICAL INTERVENTION •NERVE TERMINAL • Neurotransmitter release •POST SYNAPTIC MEMBRANE • Neurotransmitter-receptor interaction •NEUROTRANSMITTER EFFECT TERMINATION • Neurotransmitter degradation ANS drugs • Drugs can selectively mimic (agonists) or inhibit (antagonists) ANS responses at receptors • Some are therapeutically useful – Muscarinic antagonist (all mAChR): Atropine • Blocks muscarinic receptor • Blocks parasympathetic actions at effector tissues • Reduces salivary and bronchial secretion (e.g. during surgery) ‒ Adrenergic agonist: Salbutamol • Activates b2 adrenergic receptors • Dilates bronchioles – treatment of asthma / COPD • Lack of effect at b1 means no effect on heart ‒ Adrenergic antagonist: Atenolol • Blocks b1 adrenergic receptors • CVS: Lowers blood pressure - treatment of hypertension AUTONOMIC DYSFUNCTION • Dysautonomia – Many forms: Orthostatic hypertension, neurocardiogenic syncope, chronic stress disorders (chronic activation of HPA (hypothalamic-pituitary-adrenal) axis) – Trauma, Inflammation, Drugs, Neurodegenerative disease • E.g. deficiency of sympathetic activity due to lesion /compression (trauma, tumor) in Horner’s syndrome: drooping eyelid (ptosis) + constriction of pupil (miosis) together with anhydrosis (decreased sweating) Images: www.emergencyMedicineIreland.com/Wikpediacomm COMPARISON OF AUTONOMOUS AND SOMATIC NS Books that could help… • Neuroscience: exploring the brain. Bear, Connors, Paradiso • 3rd edition. Parts of chapter 5, 6, and 15 • Boron, Boulpaep, Medical Physiology ( https://www-clinicalkey-com.proxy.library.rcsi.ie/#!/content/book/3s2.0-B9781455743773000148 ) • Rhoades, Medical Physiology, Principles for Clinical Medicine (http://meded.lwwhealthlibrary.com.proxy.library.rcsi.ie/content.as