Autonomic Nervous System Physiology 2024-25 PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Autonomic Nervous System Biology Class DEM Year 1 Course The Body: Movement and Function (BMF) Lecturer Dr. Ebrah...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Autonomic Nervous System Biology Class DEM Year 1 Course The Body: Movement and Function (BMF) Lecturer Dr. Ebrahim Rajab ([email protected]) Date 10/11/2024 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 and parasympathetic nervous systems  Describe the neurotransmitters and receptors located in the ANS 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 autonomic nervous the enteric system nervous uses system is a 3rd division: vast different network of nerve fibers 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 or when stress involved (sudden Restorative/maintenance of the body burst of energy required) – „Rest & Digest“ – „Fight or Flight“ – Increases cardiac output and – allows us to unwind and conserve pulmonary ventilation, routes energy blood to muscles, raises blood – Promotes secretions and mobility of glucose and slows down digestion, kidney filtration and other functions different parts of the digestive tract not needed during emergencies – Also involved in urination, defecation – Whole of sympathetic system tends – (parts of…) Parasympathetic (NS) to "go off" together 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 Example: or flight’ Sympathetic stimulation increases heart rate whereas parasympathetic stimulation decreases it Usually both systems are partially active, due to some level of basal activity in both the sympathetic and parasympathetic supplying a particular organ 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  Arrangement of SNS & PSNS pathways Each ANS pathway Parasympathetic Preganglionic fibres are long and myelinated from CNS to Postganglionic nerves are short and unmyeli organ/effector is Parasympathetic Cranial Postganglionic fibre two-neuron chain Sacral Preganglionic fibre Effector organ (neuron- ganglion synapse/ganglion -neuron) Sympathetic i.e., CNS → Thoracic Preganglionic fibre Postganglionic fibre Lumbar Effector organ preganglionic nerve CNS → ganglion → ganglion Sympathetic postganglionic Preganglionic fibres are short and myelinate Postganglionic nerves are long and unmyelina nerve → organ Modified Sympathetic Nervous System – Adrenal Medulla Two adrenal glands: „Ad“ „renal“ - next to kidney Consists of Outer adrenal cortex and Inner adrenal medulla Extension of sympathetic nervous system 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=epinephrine 80% / Noradrenaline=norepinephrine20%) directly into the blood 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 post- ganglionic neuron Sympathetic Nervous System “Thoracolumbar outflow” – Preganglionic: thoracic and lumbar regions of spinal cord (T1 – L3) – Sympathetic preganglionic nerves are short and myelinated) – Sympathetic ganglia lie in a (sympathetic trunk/)chain along either side of spinal cord – Sympathetic postganglionic nerves are long (and 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 Each ACh 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: – Cholinergic receptors: Binds and responds to acetylcholine (ACh) – Adrenergic receptors: Binds and responds to adrenaline and noraderenaline  Additional complexity and exceptions to the rules Salivary glands secretion increased via both sympathetic and parasympathetic input Blood vessels Resistance vessels (Arterioles) innervated by sympathetic NS only Sweat glands Mainly sympathetic innervation and terminal fibre release ACh(!) not NA(!) Neurotransmitter (NT) receptors of 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 Receptors can be ionotropic or metabotropic  Ionotropic receptors 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 Neurotransmitter (NT) released from pre-ganglionic/synaptic cell/neuron 1 Ionotropic receptor 2 Metabotropic receptor + (G-protein coupled) + + + + + + + - - ++ - - - a - - ++ b 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 (hence the  name) Ionotropic, thus fast respons  *Subtypes NN or N2  (NM or N1 at skeletal muscle NM Cholinergic Receptors: nicotinic vs muscarinic MUSCARINIC type: Found on effector cell membranes e.g. smooth muscle, glands, cardiac muscle Receptor activated by ACh released from postganglionic parasympathetic nerves Receptor activated by mushroom poison muscarine 5 types of muscarinic ACh receptor (M1-5) All G protein-coupled metabotropic receptors - Nicotinic Receptors – ACh binding opens Pre-ganglionic fibre intrinsic Na+/K+ channel Nicotinic ACh receptor is ACh ionotropic Na+ – Resulting in ANS ganglion Nicotinic receptor depolarisation of ++ ++ postsynaptic cell – Response is rapid Post-ganglionic fibre – New action potential transmitted  Muscarinic Receptors muscarinic ACh receptors are metabotropic 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 NT receptors: Parasympathetic division Now consider parasympathetic stimulation of a tissue/organ… Muscarinic receptor Effector ACh tissue/organ Na+ Parasympathetic Nicotinic e.g. cAMP ganglion receptor ++ ++ e.g. PKA Post-ganglionic fibre Cell response e.g. reduced heart rate Adrenergic Receptors - types Only found at effector organ synapses After postganglionic sympathetic nerves Two major classes ( and ) that bind noradrenaline and adrenaline All of these types couple to G proteins but intracellular coupling differs Adrenergi c a-adrenergic b-adrenergic a1 a2 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 vascular beds, smooth muscle of some vessels & organs Couples via G protein to cyclic AMP/PKA e.g. relaxation of smooth muscle → skeletal muscle arteriolar dilation and bronchiolar dilation Effector organs/tissues express receptors for the NT of both types of postganglionic fibres Postganglionic Postganglionic parasympathetic nerve sympathetic nerve ACh Synapse 1 Synapse 2 musAChR NA NA-R reduced increased contraction 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 AChE ACh receptors Termination of NT effects NA is re-uptaken by pre- and post- synaptic 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) – Due to 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/3- s2.0-B9781455743773000148 ) Rhoades, Medical Physiology, Principles for Clinical Medicine (http://meded.lwwhealthlibrary.com.proxy.library.rcsi.ie/content.as