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Autonomic Nervous System http://www.michiganneurology.com Note Much of the text material is from, “Principles of Anatomy and Physiology” by Gerald J. Tortora and Bryan Derrickson (2009, 2011, and 2014). I don’t claim authorship. Other sources are noted when they are used. The lecture slides are mapped to the three editions of the textbook based on the color-coded key below. 14th edition 13th edition 12th edition Same figure or table reference in all three editions 2 Outline • • • • • • Basic principles More detail on motor control Neurotransmitters and receptors Physiological responses Autonomic integration and control Two medical conditions 3 Basic Principles 4 Autonomic Nervous System • The autonomic nervous system (ANS) responds to certain types of visceral sensations and excites or inhibits effectors to control some bodily functions. • Effectors include smooth muscle, cardiac muscle, and endocrine and exocrine glands. Visceral = pertaining to organs or tissue coverings of organs. Page 523 Page 581 Page 546 5 Autonomic Nervous System • The ANS consists of sensory neurons, integrative centers in the brain and spinal cord, and motor neurons. • It operates via lower- and higher-level reflex arcs, and almost always without conscious awareness or conscious control. Effector = a muscle, gland, or organ capable of responding to a stimulus, especially action potentials. Page 523 Page 581 Page 546 6 Divisions • The motor (output) components of the ANS are the sympathetic and parasympathetic divisions. • Most organs receive input from both ANS divisions—this is known as dual innervation. • The divisions often, but not always, work in opposition to one another. Page 524 Page 582 Page 547 7 Divisions (continued) http://www.yesselman.com 8 Divisions (continued) • Action potentials from one division stimulate the organ to increase its activity (excitation). • Action potentials from the other division decrease the organ’s activity (inhibition). • For example, sympathetic activation increases and parasympathetic activation decreases heart rate. • In a few instances, the two divisions work together, such as the male sexual response. Page 524 Page 582 Page 547 9 Control • The ANS was originally named “autonomic” because it was thought to function autonomously of brain function. • Nuclei in the hypothalamus and brainstem are now known to be involved in regulating its motor activity. Autonomous = self-governing; independent; free of external influence or control. Page 524 Page 582 Page 547 10 Limited Conscious Control • Due to the lack of sensory awareness, very few autonomic responses can be consciously altered. • Consider, however: Practitioners of yoga and other meditative techniques can learn from long and diligent practice how to regulate some autonomic functions, such as heart rate. - Biofeedback using electronic monitoring can provide sensory feedback to enhance the ability to exert some conscious control of ANS functions. - Page 524 Page 582 Page 547 11 http://counseling.ucr.edu Biofeedback 12 Sensory Input • Most sensory input is from sensory neurons located in blood vessels, visceral organs, and muscles. • The sensory neurons are called interoreceptors since they respond to internal sensations. • They include mechanoreceptors to detect stretch in the walls of hollow organs and blood vessels, and chemoreceptors to monitor blood CO2 level. Page 524 Page 582 Page 547 13 Sensory Input (continued) • The sensory signals from interoreceptors are generally not consciously perceived since they usually don’t reach the level of the cerebral cortex. • Intense activation of interoreceptors can, however, produce conscious sensations. • For example, inadequate coronary blood flow can result in chest pain known as angina pectoris. • Somatic (body) sensations can sometimes affect the ANS—for example, intense pain can produce changes in autonomic activity such as in heart rate. Page 524 Page 582 Page 547 14 Other Sensory Inputs • The special senses acting through the limbic system can also affect autonomic responses. • For example, the reaction to an unexpectedly loud noise can include an increased heart rate in a physiological response known as sympathetic arousal. • We will discuss this fight or flight response later in the lecture. Page 524 Page 582 Page 547 15 Motor Output • Autonomic motor neurons regulate visceral activities by either increasing (exciting) or decreasing (inhibiting) the physiological actions of their effectors. • ANS motor responses include changes in the diameter of the pupils, changes in heart rate, and dilation and constriction of blood vessels. • Unlike skeletal muscle tissue, tissues innervated by the ANS can function autonomously to some extent if their nerve supply is damaged. ANS effectors = cardiac muscle, smooth muscle, and endocrine and exocrine glands. Innervation = to supply an organ or a body part with nerves. Page 524 Page 582 Page 547 16 Motor Pathways • An autonomic motor pathway has two motor neurons positioned in series. • The cell body of the first neuron is located in the CNS—its myelinated axon extends to an autonomic ganglion positioned outside of the CNS. • The cell body of the second neuron is located in the autonomic ganglion—its unmyelinated axon extends to an effector. • An exception to this rule is the axon of the first motor neuron extends directly to chromaffin cells in the adrenal medulla—there is no second neuron. Ganglion (plural, ganglia) = collection of cell bodies of neurons outside of the CNS. Page 524 Page 582 Page 547 17 Motor Pathways (continued) Neuron 1 Neuron 2 Axon Effector Cell body and dendrites Synapse (dendrites are not shown) Schematic diagram = a drawing intended to explain how something works. 18 Motor Pathways (continued) Preganglionic neuron Postganglionic neuron Myelinated axon Unmyelinated axon Effector Smooth muscle Cardiac muscle Endocrine and exocrine glands Central nervous system Peripheral nervous system (postganglionic neuron) 19 Neurotransmitters • Somatic motor neurons release acetylcholine (ACh) at the neuromuscular junctions (synapses) with skeletal muscles. • Autonomic motor neurons release either ACh or norepinephrine (NE) at their synapses. • More detail will be provided as we proceed with this lecture material. Page 524 Page 582 Page 547 20 More Detail on Motor Control 21 Motor Pathways • As discussed, the cell body of an ANS preganglionic neuron is located in the brain or spinal cord (central nervous system). • Its axon—a small-diameter, myleninated type B fiber—exits the CNS as part of a cranial nerve or spinal nerve. • The axon extends to an autonomic ganglion in the PNS, where it synapses with a postganglionic neuron. Page 526 Page 584 Page 549 Figure 15.1 22 Motor Pathways (continued) • The axon of the postganglionic neuron is a small-diameter, unmyleninated type C fiber. • The axon synapses with an effector, which could be smooth muscle, cardiac muscle, or endocrine or exocrine gland. Page 526 Page 584 Page 549 Figure 15.1 23 Parasympathetic Preganglionic Neurons • In the parasympathetic division, cell bodies of preganglionic neurons are found in the nuclei of cranial nerves III, VII, IX, and X, and sacral segments 2 through 4. • The parasympathetic division is therefore also known as the craniosacral division. III—Oculomotor nerve VII—Facial nerve IX—Glossopharyngeal nerve X—Vagus nerve Page 529 Page 584 Page 549 Figure 15.3 24 Sympathetic Preganglionic Neurons • The cell bodies of the preganglionic neurons are located in the lateral horns of the 12 thoracic segments and the first 2 to 3 lumbar segments of the spinal cord. • The sympathetic division is therefore also known as the thoracolumbar division. Page 526 Page 584 Page 549 Figure 15.2 25 http://www.microscopy-uk.org.uk Lateral Horn of Spinal Cord WM = white matter; GM = gray matter. 26 Autonomic Ganglia • The autonomic ganglia differ in location and structure in the parasympathetic and sympathetic divisions. • Parasympathetic division—the ganglia are found close to, or in the walls of, visceral organs. • Sympathetic division—the ganglia form an interconnected chain of cell bodies and axons, known as the sympathetic ganglionic chain, in close proximity to the spinal cord. Page 529 Page 587 Page 549 Figure 15.2 Figure 15.3 27 Axon Lengths • Parasympathetic division—long preganglionic axons and short postganglionic axons. • Sympathetic division—almost always short preganglionic axons and long postganglionic axons. • We will discuss the functional significance of these structural differences. Page 529 Page 587 Page 549 Figure 15.2 Figure 15.3 28 Comparison of Axon Lengths Parasympathetic division: Long Short Effector Sympathetic division: Short Long Effector Preganglionic neuron Postganglionic neuron 29 Parasympathetic Postganglionic Neurons • One parasympathetic preganglionic neuron can synapse with up to 4 to 5 postganglionic neurons. • Each postganglionic axon, however, only innervates only one effector. • This anatomical arrangement enables parasympathetic responses to be localized to one or possibly a few organs. Page 529 Page 587 Page 549 Figure 15.3 30 Sympathetic Postganglionic Neurons • A sympathetic preganglionic neuron can synapse with 20 or more postganglionic neurons. • The sympathetic ganglionic chain also enables action potentials to propagate up and down the chain. • A postganglionic axon can therefore innervate many different effectors in different parts of the body. • Wide divergence helps explain why sympathetic activation simultaneously affects much of the body. Page 529 Page 587 Page 549 Figure 15.2 31 Neurotransmitters and Receptors 32 Cholinergic and Adrenergic Neurons • Autonomic neurons are classified as cholinergic or adrenergic based on the neurotransmitter synthesized and released at their synapses. • Receptors, made-up of proteins, are found on the plasma membrane of the postsynaptic neuron or effector cell. Cholinergic = acetylcholine (ACh) is the neurotransmitter. Adrenergic = norepinephrine (NE) is the neurotransmitter. Page 535 Page 593 Page 558 Figure 15.7 33 Cholinergic and Adrenergic Neurons (continued) Parasympathetic division: Cholinergeric Cholinergeric Effector Sympathetic division: Cholinergeric Adrenergic (usually) Effector Preganglionic neuron Postganglionic neuron Cholinergic = acetylcholine Adrenergic = norepinephrine 34 Cholinergic Neurons • Cholinergic neurons in the two divisions of the autonomic nervous system include: All preganglionic neurons in the parasympathetic and sympathetic divisions. - All postganglionic neurons in the parasympathetic division. - Postganglionic neurons in the sympathetic division that innervate exocrine (sweat) glands in the skin. - Page 535 Page 593 Page 558 Figure 15.7 35 http://thebrain.mcgill.ca Synapse 36 Cholinergic Neurons (continued) • ACh, stored in the synaptic vesicles of the end buttons of axons, is released via exocytosis in response to action potentials. • ACh diffuses across the synaptic cleft and binds to the cholinergic receptors on the postsynaptic membrane to produce graded potentials. • Cholinergic receptors are either called nicotinic or muscarinic based on certain unique properties. Page 535 Page 593 Page 558 Figure 15.7 37 Tobacco Plant http://etc.usf.edu 38 Nicotinic Receptors • Nicotinic cholinergic receptors respond to nicotine, a chemical not naturally found in the human body. • Small amounts of nicotine, when introduced at nicotinic synapses, binds to the postsynaptic receptors, and mimics the action of ACh. • The activation of nicotinic receptors produces depolarizing graded potentials. Page 535 Page 593 Page 558 Figure 15.7 39 Nicotinic Receptors (continued) • Nicotinic receptors are found in the: Preganglionic neurons of the parasympathetic and sympathetic divisions. - Chromaffin cells of the adrenal medulla innervated by the sympathetic division. - Neuromuscular junctions in skeletal muscle (which are innervated by somatic motor neurons). - Page 535 Page 593 Page 558 Figure 15.7 40 http://ciuperci.org Amanita muscaria Muscarine is found in some species of mushrooms, including Amanita muscaria. Its ingestion can result in intense parasympathetic responses, convulsions, and death. 41 Muscarinic Receptors • Muscarinic cholinergic receptors are named for a mushroom toxin known as muscarine. • Muscarine mimics the action of ACh when binding to postsynaptic receptors. • These receptors are found in smooth muscle, cardiac muscle, and glands innervated by postganglionic axons of the parasympathetic division. • Most sweat glands innervated by postganglionic axons of the sympathetic division have muscarinic receptors. Page 535 Page 593 Page 558 Figure 15.7 42 Muscarinic Receptors (continued) • Stimulation of muscarinic receptors produces depolarizing or hyperpolarizing graded potentials based on the effector cell type. • The binding of ACh to the muscarinic receptors in the digestive tract inhibits (relaxes) its smooth muscle sphincters. • ACh excites the muscarinic receptors in the smooth muscle fibers of the iris of the eye, causing the smooth muscles to contract and decrease pupil size. Page 537 Page 593 Page 558 Figure 15.7 43 Adrenergic Neurons • Adrenergic neurons release norepinephrine (sometimes called noradrenalin). • Most postganglionic neurons in the sympathetic division are adrenergic, except those that innervate sweat glands in the skin. Page 536 Page 594 Page 559 Figure 15.7 44 Adrenergic Neurons (continued) • Norepinephrine is stored in synaptic vesicles and is released via exocytosis in response to action potentials from sympathetic postganglionic neurons. • Norepinephrine diffuses across the synaptic cleft and binds to the adrenergic receptors in the postsynaptic membrane of the effector cell. • A depolarizing or hyperpolarizing graded potential results, depending on the cell type. Page 536 Page 594 Page 559 Figure 15.7 45 Norepinephrine and Epinephrine • Adrenergic receptors in the postsynaptic membrane bind norepinephrine and epinephrine (a closely-related molecule of the catecholamine family). • Most postganglionic neurons of the sympathetic division release norepinephrine. • Epinephrine and small amounts of norepinephrine are also released from the chromaffin cells of the adrenal medulla into general blood circulation (in this sense they are hormones and not neurotransmitters). http://mybrainnotes.com Page 536 Page 594 Page 559 46 Neurotransmitter Inactivation • The action of norepinephrine is terminated when it is inactivated by an enzyme (COMT or MAO) and is then reabsorbed by the end buttons of the neurons. • Norepinephrine persists in the synaptic cleft for a longer period of time than ACh since COMT and MAO are relatively slow-acting compared to acetylcholine esterase (AChE). • Therefore, the effects triggered by norepinephrine are generally longerlasting than those triggered by ACh. COMT = catechol-O-methyl transferase MAO = monoamine oxidase Page 536 Page 594 Page 559 47 Alpha and Beta Receptors • Adrenergic receptors are classified as either alpha () or beta () types. • As discussed, the receptors are found on the postsynaptic membranes of effectors innervated by most postganglionic axons in the sympathetic division. • Sweat glands are a major exception. Page 536 Page 594 Page 559 48 Alpha and Beta Receptors (continued) • Cells of most sympathetic effectors have either or receptors, although some cells can have both types. • Norepinephrine stimulates receptors more strongly than it stimulates receptors. • Epinephrine, in comparison, is a strong stimulator of both and receptors. Page 536 Page 594 Page 559 49 Receptor Subtypes • Alpha and beta receptors have subtypes—they are 1, 2, 1, 2, and 3. • The classification is based on the responses they trigger, and the selective binding of drugs that can activate or block the receptors. • The 1 and 1 receptors generally produce excitation while 2 and 2 receptors produce inhibition of effector cells. • The 3 receptors are limited to brown adipose cells where activation produces thermogenesis. Thermogenesis = the production of heat, especially within an animal body. Page 536 Page 594 Page 559 50 Receptor Agonists • Certain drugs and natural substances selectively activate or block cholinergic and adrenergic receptors. • An agonist is a substance that binds to and activates receptors in the postsynaptic membrane to mimic the effect of the neurotransmitter or hormone. • Phenylephrine, a common ingredient in cold and sinus medications, is an agonist of 1 receptors. • The drug constricts blood vessels in the nasal mucosa to reduce the production of mucus and relieve nasal congestion. Page 536 Page 594 Page 560 51 Receptor Antagonists • An antagonist is a substance that binds to and blocks receptors to prevent a neurotransmitter or hormone from exerting its effect. • Atropine blocks mucarinic (ACh) receptors—it dilates the pupils, reduces glandular secretions, and relaxes smooth muscle of the digestive tract. • Atropine is used to dilate the pupils during eye exams by optometrists and ophthalmologists. • It is also used as an antidote for certain chemical warfare agents (such as nerve gas) that trigger massive amounts of ACh release. Page 536 Page 594 Page 560 52 Physiological Responses 53 Autonomic Tone • Most body organs are innervated by the parasympathetic and sympathetic divisions. • The two divisions usually, but not always, work in opposition to one another. • The balance of activity between the two divisions, called autonomic tone, is regulated by the hypothalamus. Page 536 Page 596 Page 560 54 Autonomic Tone (continued) • The two divisions can affect the same body organs differently because: The postganglionic neurons release different neurotransmitters. - Effector organs can have cholinergic and adrenergic receptors. - Page 537 Page 596 Page 560 55 Sympathetic Responses • The sympathetic division dominates during physical activities and emotional stress. • Sympathetic activation favors body functions that support physical activities, including fight or flight, as will be discussed in upcoming slides. • It also reduces body functions involved in the storage of potential energy from food—sympathetic activation slows down the digestive process. Page 537 Page 596 Page 560 56 Sympathetic Responses (continued) • Strong emotions such as fear, embarrassment, and rage can stimulate the sympathetic division. • Sympathetic activation and the release of norepinephrine and epinephrine from the adrenal medulla set in motion a complex series of physiological responses. • The changes collectively are known as the fight or flight response, which can be triggered by an intense stressor. Stressor = a condition or agent that causes physiological or psychological stress to an organism. Page 537 Page 596 Page 560 57 Fight or Flight http://www.uh.edu http://darwin-online.org.uk 58 Fight or Flight Response • The fight or flight response produces a wide range of physiological changes, including: Dilation of the pupils. - Dilation of the bronchioles (small air passageways) to improve airflow. - Increased heart rate, force of cardiac contraction, and blood pressure to increase cardiac output. - Page 538 Page 596 Page 560 59 Fight or Flight Response (continued) • The physiological changes also include Dilation of blood vessels to the skeletal muscles, cardiac muscle, and liver to increase blood flow. - Constriction of blood vessels to the kidneys and digestive tract to reduce blood flow. - Slowing-down of non-essential processes, including the smooth muscle activity in the digestive tract. - Page 538 Page 596 Page 560 60 Fight or Flight Response (continued) • Additional physiological changes include: Breakdown of glycogen to glucose in the liver (glycogenolysis). - Release of the glucose from the liver to serve as an immediate source of energy for anaerobic respiration in other body tissues. - Breakdown of trigylcerides to glycerol and fatty acids (lipolysis) to serve as a chemical energy source for aerobic respiration. - Page 538 Page 596 Page 560 61 Sympathetic Scope and Persistence • The effects of sympathetic activation, such as in the fight or flight response, are more widespread and longer lasting than the effects of parasympathetic activation. • The postganglionic axons of the sympathetic division diverge more extensively, and therefore many different tissues are activated simultaneously. • Epinephrine and norepinephrine are also secreted by the adrenal medulla into general blood circulation, which serve to intensify and prolong sympathetic responses. • COMT and MAO are slower to break-down norepinephrine and epinephrine than the action of AChE on acetylcholine, to enable sympathetic responses to persist longer. Page 537 Page 596 Page 560 62 Sympathetic Inactivation • Norepinephrine and epinephrine are eventually inactivated by enzymes in the liver. • The metabolites are recycled for the re-synthesis of catecholamines. Catecholamine = an amine derived from the amino acid tyrosine that act as a neurotransmitter or hormone; includes norepinephrine, epinephrine, and dopamine. Page 538 Page 596 Page 560 63 Parasympathetic Responses • The parasympathetic division enhances the so-called rest and digest activities. • The activities support body functions to conserve and restore energy during periods of rest and recovery. Page 538 Page 596 Page 561 64 Parasympathetic Activation (continued) • The ungainly acronym, SLUDD can used to recall the five major parasympathetic responses. • These responses are: 1) salivation, 2) lacrimation, 3) urination, 4) digestion, and 5) defecation. • Other parasympathetic responses include decreased heart rate, decreased diameter of the airways, and constriction of the pupils. • Parasympathetic activation is also involved in sexual arousal. Lacrimation = secretion of tears. Page 539 Page 597 Page 561 65 Autonomic Integration and Control 66 Autonomic Reflexes • Autonomic reflexes have a major role in regulating body functions including: Blood pressure, by regulating heart rate, force of ventricular contraction of the heart, and diameter of blood vessels. - Digestion, by regulating smooth muscle tone and motility of the digestive tract. - Defecation and urination, by regulating the opening and closing of smooth muscle sphincters. - Motility = motion or movement. Page 540 Page 599 Page 562 67 Components of an Autonomic Reflex Arc • Receptor—distal end of a sensory neuron (often an interoreceptor) • Sensory neuron—cell body and axon. • Integrative center in the spinal cord or brainstem—interneurons • Motor neurons • Effector—smooth muscle, cardiac muscle, or endocrine or exocrine gland Page 540 Page 599 Page 562 68 Autonomic Reflex Arcs Sympathetic division Parasympathetic division http://www.medical-look.com 69 Hypothalamic Control • The hypothalamus is the key integrative and control center for the autonomic nervous system. • It receives sensory input from visceral functions, smell (olfaction), and taste (gustation). • It also receives input for body temperature, osmolarity, and concentration of various substances in the blood including glucose. • The hypothalamus also receives input from the limbic system for emotional states. Osmolarity = a measure of the concentration of a solution. Page 541 Page 601 Page 563 70 Hypothalamic Control (continued) • Nuclei in the anterior and medial areas of the hypothalamus control the parasympathetic division. • Nuclei in the posterior and lateral areas control the sympathetic division. • Output from these autonomic centers is to the brainstem and spinal cord. Page 541 Page 601 Page 563 71 Two Medical Conditions 72 Raynaud’s Phenomenon • In Raynaud’s phenomenon, the fingers and toes become ischemic in response to the thermal sensations of cold or to emotional stress. • The symptoms result from excessive sympathetic stimulation of the smooth muscle in the arterioles of the digits, constricting the blood vessels and reducing blood flow. • People with Raynaud’s phenomenon often have low blood pressure. Ischemia = a decrease in the blood supply and therefore oxygen to a body organ or tissue due to constriction or obstruction of the blood vessels. Arteriole = small branch of an artery that connects with a capillary. Digits = fingers and toes. Page 541 Page 601 Page 565 73 Raynaud’s Phenomenon (continued) http://www.nlm.nih.gov 74 Raynaud’s Phenomenon (continued) • Some people who have Raynaud's phenomenon have an increased number of -adrenergic receptors. • The phenomenon is most common in young woman, and is observed most often in cold climates. • Treatment includes use of calcium channel blockers and alpha receptor blockers to relax the smooth muscles in the arteriole walls and improve blood flow. • Smoking, alcohol, and some illicit drugs can exacerbate the symptoms. Page 541 Page 601 Page 565 75 Autonomic Dysreflexia • Autonomic dysreflexia is an exaggerated response of the sympathetic division in persons who have spinal cord injuries at or above T6 (the sixth thoracic segment). • The condition is due to interruption of ANS control by the hypothalamus. Page 541 Page 601 Page 565 76 Autonomic Dysreflexia (continued) • Sensory nerve impulses, such as from a full urinary bladder, stimulate the sympathetic nerves inferior to the injured level of the spinal cord. • Other triggering events (or stimuli) include: Stimulation of pain receptors below the spinal cord injury - Bowel distension - Smooth muscle contractions from sexual stimulation - Labor and delivery - Page 541 Page 601 Page 565 77 Autonomic Dysreflexia (continued) • Autonomic dysreflexia triggers a complex chain of events and feedback mechanisms in the parasympathetic and sympathetic divisions. • The condition is characterized by: Pounding headache - Anxiety - Flushed, warm skin with profuse sweating above the level of injury - Pale, cold, and dry skin below the injury level - • Because the condition can be life-threatening, it requires immediate medical intervention, including identifying and removing the stimulus. Page 541 Page 601 Page 565 78