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Autonomic Response ? Peshawar Medical College NWFP Pakistan Autonomic Nervous System Part of the Nervous system that Controls most of the Visceral Functions of the Body ( Automatically ? ) Peshawar Medical College NWFP Pakistan Classification Of CNS Peshawar Medical College NWFP Pakistan Autonomic Nervous System • Visceral functions – Heart and Blood Pressure – GIT motility & Secretions – Urinary Bladder emptying – Sweating & Body Temperature regulation – Bronchodilation and Constriction – Muscle Blood flow • Rapidity & Intensity – Functions within seconds Peshawar Medical College NWFP Pakistan Autonomic Nervous System • Higher control: – Spinal cord – Brain Stem – Hypothalamus – Limbic System • Visceral Reflexes- Subconscious Reflex Response Peshawar Medical College NWFP Pakistan Typical Spinal Nerve Peshawar Medical College NWFP Pakistan Peshawar Medical College NWFP Pakistan Peshawar Medical College NWFP Pakistan Physiologic Anatomy of the Sympathetic Nervous System Paravertebral sympathetic chains of ganglia • Prevertebral ganglia (collateral ganglia) are sympathetic ganglia which lie between the paravertebral ganglia and the target organ. • Nerves extending from the ganglia to the different internal organs. Peshawar Medical College NWFP Pakistan • The sympathetic nerve fibers originate in the spinal cord along with spinal nerves between cord segments T-1 and L-2 and pass first into the sympathetic chain and then to the tissues and organs that are stimulated by the sympathetic nerves. Peshawar Medical College NWFP Pakistan Peshawar Medical College NWFP Pakistan • The cell body of each preganglionic neuron lies in the intermediolateral horn of the spinal cord; its fiber passes,through an anterior root of the cord into the corresponding spinal nerve. Peshawar Medical College NWFP Pakistan • Immediately after the spinal nerve leaves the spinal canal, the preganglionic sympathetic fibers leave the spinal nerve and pass through a white ramus into one of the ganglia of the sympathetic chain. Peshawar Medical College NWFP Pakistan • Then the course of the fibers can be one of the following three: • (1) It can synapse with postganglionic sympathetic neurons in the ganglion that it enters. • (2) it can pass upward or downward in the chain and synapse in one of the other ganglia of the chain. Peshawar Medical College NWFP Pakistan • (3) it can pass for variable distances through the chain and then through one of the sympathetic nerves radiating outward from the chain, finally synapsing in a peripheral sympathetic ganglion. Peshawar Medical College NWFP Pakistan • The postganglionic sympathetic neuron thus originates either in one of the sympathetic chain ganglia or in one of the peripheral sympathetic ganglia. • From either of these two sources, the postganglionic fibers then travel to their destinations in the various organs. Peshawar Medical College NWFP Pakistan • The splanchnic nerves are paired visceral nerves (nerves that contribute to the innervation of the internal organs), carrying fibers of the autonomic nervous system (visceral efferent fibers) as well as sensory fibers from the organs (visceral afferent fibers). • Thoracic splanchnic nerves are splanchnic nerves that arise from the sympathetic trunk Peshawar Medical College NWFP Pakistan Peshawar Medical College NWFP Pakistan Sympathetic Nerve Fibers in the Skeletal Nerves. • Some of the postganglionic fibers pass back from the sympathetic chain into the spinal nerves through gray rami at all levels of the cord. • These sympathetic fibers are all very small type C fibers, and they extend to all parts of the body by way of the skeletal nerves. Peshawar Medical College NWFP Pakistan • They control the blood vessels, sweat glands, and piloerector muscles of the hairs. • About 8 per cent of the fibers in the average skeletal nerve are sympathetic fibers. Peshawar Medical College NWFP Pakistan Peshawar Medical College NWFP Pakistan Peshawar Medical College NWFP Pakistan Segmental Distribution of the Sympathetic Nerve Fibers. The sympathetic fibers from cord segment: T-1 pass up the sympathetic chain to terminate in the head; T-2 to terminate in the neck; T-3, T-4, T-5, and T-6 into the thorax; T-7, T-8, T-9, T-10 &T-11 into the abdomen; T-12, L-1 & L-2 into the legs. Peshawar Medical College NWFP Pakistan Special Nature of the Sympathetic Nerve Endings in the Adrenal Medullae. Preganglionic sympathetic nerve fibers pass, without synapsing, all the way from the intermediolateral horn cells of the spinal cord, through the sympathetic, then through the splanchnic nerves, and finally into the two adrenal medullae. There they end directly on modified neuronal cells that secrete epinephrine and norepinephrine into the blood stream. Peshawar Medical College NWFP Pakistan Physiologic Anatomy of the Parasympathetic Nervous System • Parasympathetic fibers leave the central nervous system through: • cranial nerves III(Oculomotor), • VII( Facial), IX(Glossophyrangeal), • and X( Vagus); • Additional parasympathetic fibers leave the lowermost part of the spinal cord through the S2 & S3 sacral spinal nerves. Peshawar Medical College NWFP Pakistan • About 75 per cent of all parasympathetic nerve fibers are in the vagus nerves (cranial nerve X), passing to the entire thoracic and abdominal regions of the body. Peshawar Medical College NWFP Pakistan Peshawar Medical College NWFP Pakistan • The vagus nerves supply parasympathetic nerves to the • Heart, • Lungs, • Esophagus, • Stomach, • Entire small intestine, • Proximal half of the colon, • Liver, Gallbladder, Pancreas, Kidneys, and • Upper portions of the ureters. Peshawar Medical College NWFP Pakistan • Parasympathetic fibers in III cranial nerve go to the pupillary sphincter and ciliary muscle of the eye. • Fibers from VII cranial nerve pass to the lacrimal, nasal, and submandibular glands. Fibers from IX cranial nerve go to the parotid gland. Peshawar Medical College NWFP Pakistan • Sacral parasympathetic fibers are in the pelvic nerves, which pass through the spinal nerve sacral plexus on each side of the cord at the S-2 and S-3 levels. Peshawar Medical College NWFP Pakistan • • • • • • These fibers then distribute to the: Descending colon, Rectum, Urinary bladder, and Lower portions of the ureters. This sacral group of parasympathetics supplies nerve signals to the external genitalia to cause erection. Peshawar Medical College NWFP Pakistan Preganglionic and Postganglionic Parasympathetic Neurons • The parasympathetic system, like the sympathetic, has both preganglionic and postganglionic neurons. • The preganglionic fibers pass uninterrupted all the way to the organ that is to be controlled. • . Peshawar Medical College NWFP Pakistan • In the wall of the organ are located the postganglionic neurons. • The preganglionic fibers synapse with very, very short postganglionic fibers, a fraction of a millimeter to several centimeters in length. Peshawar Medical College NWFP Pakistan Parasympathetic Division Cranial Nerves III - Occulomotor N VII- Facial N IX - Glossopharyngeal N X - Vagus N Sacral Outflow: S1 – S4 Peshawar Medical College NWFP Pakistan Peshawar Medical College NWFP Pakistan 36 Peshawar Medical College NWFP Pakistan 37 Peshawar Medical College NWFP Pakistan Basic Characteristics Cholinergic & Adrenergic Fibers Peshawar Medical College NWFP Pakistan Peshawar Medical College NWFP Pakistan • The sympathetic and parasympathetic nerve fibers secrete mainly one or the other of two synaptic transmitter substances, acetylcholine or norepinephrine. • Those fibers that secrete acetylcholine are said to be cholinergic. • Those that secrete norepinephrine are said to be adrenergic, a term derived from adrenalin, which is an alternate name for epinephrine. Peshawar Medical College NWFP Pakistan Sympathetic Cholinergic Parasympathetic Cholinergic Cholinergic Sweat Glands, Piloerector Muscle, A few Blood Vessels Adrenergic Cholinergic Peshawar Medical College NWFP Pakistan Acetylcholine is called a parasympathetic transmitter. Norepinephrine is called a sympathetic transmitter. Peshawar Medical College NWFP Pakistan Peshawar Medical College NWFP Pakistan Other Neurotransmitters • Dopamine • GnRH (Gonadotrophin Releasing Hormone) • Co-transmitters – VIP – Neuropeptide Y Peshawar Medical College NWFP Pakistan Mechanisms of Transmitter Secretion and Removal at Postganglionic Endings: Secretion of Acetylcholine and Norepinephrine by Postganglionic Nerve Endings Peshawar Medical College NWFP Pakistan • many of the parasympathetic nerve fibers and almost all the sympathetic fibers merely touch the effector cells of the organs • Where these filaments touch or pass over or near the cells to be stimulated, they usually have bulbous enlargements called varicosities • Here Neurotransmitters are synthesized and stored Peshawar Medical College NWFP Pakistan Release of autonomic neurotransmitters in Smooth Muscle Peshawar Medical College NWFP Pakistan • varicosities have large numbers of mitochondria that supply adenosine triphosphate, which is required to energize acetylcholine or norepinephrine synthesis. Peshawar Medical College NWFP Pakistan An action potential spreads over the terminal fibers--- the depolarization process increases the permeability of the fiber membrane to calcium ions---allowing these ions to diffuse into the nerve terminals or nerve varicosities. The calcium ions -- cause the terminals or varicosities to empty their contents to the exterior. Peshawar Medical College NWFP Pakistan • Acetyl-CoA + Choline choline acetyle transferase Acetyl choline Peshawar Medical College NWFP Pakistan • Once acetylcholine is secreted into a tissue by a cholinergic nerve ending, it persists in the tissue for a few seconds while it performs its nerve signal transmitter function. • Then it is split into an acetate ion and choline, catalyzed by the enzyme acetylcholinesterase that is bound with collagen Peshawar Medical College NWFP Pakistan Synthesis & Release of Acetylcholine Peshawar Medical College NWFP Pakistan Removal of norepinephrine: • reuptake into the adrenergic nerve endings by an active transport process, --removal of 50 to 80 percent of the secreted norepinephrine; • diffusion away from the nerve endings into the surrounding body fluids and then into the blood Peshawar Medical College NWFP Pakistan • destruction of small amounts by tissue enzymes -- monoamine oxidase, which is found in the nerve endings, • catechol-O-methyl transferase-- in the tissues Peshawar Medical College NWFP Pakistan Metabolism of Neurotransmitters • Acetylcholine – Synthesis • Norepinephrine – • From Choline • In terminal nerve endings – Destruction (enzyme) • Acetylcholinesterase Synthesis • • – From Tyrosine In axoplasm of nerve endings Removal i. Reuptake ii. Blood iii. Enzymes (MAO)& catechol-O-methyl transferase, Peshawar Medical College NWFP Pakistan Circulation of neurotransmitters • Acetylcholine: – Local • Noradrenaline/ Norepinephrine: – Local – Blood • Adrenaline/ Epinephrine – Blood – Hormone Peshawar Medical College NWFP Pakistan • RECEPTORS ON THE EFFECTOR ORGANS • acetylcholine, norepinephrine, or epinephrine bind with specific receptors on the effector cells. • The receptor is on the outside of the cell membrane ( penetrates all the way through the cell membrane) Peshawar Medical College NWFP Pakistan • Conformational change in the structure of the protein molecule-- altered protein molecule excites or inhibits the cell by (1) causing a change in cell membrane permeability to one or more ions or (2) activating or inactivating an enzyme attached to the other end of the receptor – increases the activity of the enzyme adenylyl cyclase on the inside of the cell, which causes formation of cyclic adenosine monophosphate (cAMP). Peshawar Medical College NWFP Pakistan Autonomic Receptors Receptors Cholinergic Muscarinic Adrenergic Nicotinic Alpha 1 Beta Alpha Alpha 2 Beta 1 Beta 2 Beta 3 Peshawar Medical College NWFP Pakistan Amanita muscaria, the mushroom from which muscarine was isolated Peshawar Medical College NWFP Pakistan • Muscarinic receptors are found on all effector cells that are stimulated by the postganglionic cholinergic neurons of either the parasympathetic nervous system or the sympathetic system. • Muscarinic receptors use G proteins as their signaling mechanism Peshawar Medical College NWFP Pakistan • Nicotinic receptors (ligand-gated ion channels) are found in the autonomic ganglia at the synapses between the preganglionic and postganglionic neurons of both the sympathetic and parasympathetic systems. – Also found at NMJ in Skeletal Muscles. Peshawar Medical College NWFP Pakistan Adrenergic Receptors—Alpha and Beta Receptors • use G proteins for signaling. • Norepinephrine excites mainly alpha receptors but excites the beta receptors to a lesser extent as well. • Epinephrine excites both types of receptors • relative effects are determined by the types of receptors in the organs. If they are all beta receptors, epinephrine will be the more effective excitant. • Peshawar Medical College NWFP Pakistan • alpha and beta receptors are not necessarily associated with excitation or inhibition but with the affinity of the hormone for the receptors in the given effector organ. Peshawar Medical College NWFP Pakistan Peshawar Medical College NWFP Pakistan Organs Receiving only Sympathetic Innervation • Adrenal Medulla • Kidney • Piloerrector muscles (Cholinergic) • Sweat glands (Cholinergic) • Vessels • Metabolic processes Peshawar Medical College NWFP Pakistan General Rule: Function of the autonomic nerves is dependent on the type of receptor present on the postsynaptic membrane Peshawar Medical College NWFP Pakistan Sympathetic functions Peshawar Medical College NWFP Pakistan Parasympathetic functions Peshawar Medical College NWFP Pakistan Autonomic functions Organ Parasympathetic Sympathetic EYE 1. 2. Miosis(constricted pupils) Near Accommodation (cilliary muscles constricted) 1. 2. HEART 1. 2. 3. ↓ Heart rate ↓ force of contraction ↓ Conduction of velocity Opposite (ß-1 receptors) BLOOD VESSELS 1. Dilation ? 1. Mydriasis Opposite Alpha receptors: Constriction 2. ß-2 receptors : Dilatation e.g. Coronary arteries, skeletal Peshawar Medical College NWFP Pakistanmuscles Organ Parasympathetic Lungs 1. 2. GIT Stomach, Intestine 1. ↑ Motility 2. ↑ Secretions 3. Sphincters relaxed Gall Bladder/Ducts: Contraction Opposite URINARY BLADDER 1. Opposite MTABOLISM Muscle contraction ↑ secretion 2. Detrusor Muscle Contraction Sphincter relaxed 1. Anabolism Sympathetic Opposite(ß-2) Catabolism (ß receptors) • ↑ glycogenolysis Peshawar Medical College NWFP Pakistan Organ Parasympathetic Sympathetic Kidney Nil Mental activity Nil Skeletal Muscle Nil Reduce output and Increase Renin Secretion ↑ ↑ Glycogenolysis ↑ Strength Peshawar Medical College NWFP Pakistan Autonomic Functions • Opposite to each other – Excitatory / Inhibitory • Parasympathetic: – Localized • Sympathetic: – Diffuse Peshawar Medical College NWFP Pakistan Physiological Differences B/W Adrenaline & Nor-Adrenaline Adrenalin (Epinephrine). Nor-adrenalin(Nor-Epi) 1. Greater effect on beta Receptors-Greater efffect on Heart. 2. Weak vasoconstrictor in Muscles , hence rise in TPR is less But Increase more COP. 3. 5-10 time more effect on tissue metabolism than Nor-epinephrine • 1.Less effect on Heart stimulation 2. Strong Constriction in Muscles, Hence increase in TPR is more -> Rise in BP 3. Less effect on tissue metabloism Peshawar Medical College NWFP Pakistan