Autonomic Nervous System PDF

Autonomic Nervous System José O Colón Sáez FARM-7225 Objectives • Understand the importance of the ANS. • Distinguish the characteristics of the sympathetic, parasympathetic and enteric divisions of the ANS. ✓ Components. ✓ Function. ✓ Integration with the CNS. • Identify the different neurotrans...

Autonomic Nervous System José O Colón Sáez FARM-7225 Objectives • Understand the importance of the ANS. • Distinguish the characteristics of the sympathetic, parasympathetic and enteric divisions of the ANS. ✓ Components. ✓ Function. ✓ Integration with the CNS. • Identify the different neurotransmitters and the receptors that mediate the ANS responses. Organization of the Nervous System Central nervous system • The nervous system with the endocrine system controls and coordinates various functions of the body. • The body adjust according to the changes in its internal and external environments. • These adjustments are essential for the maintenance of homeostasis, as well as for existence. Integrative function of the CNS Component Mayor Functions • Cerebral cortex Sensory perception, Voluntary movement, Language, Personality, Memory/decision making • Basal nuclei Muscle tone, Coordination slow/sustained movements. • Thalamus Inhibition of random movement Relay station for all synaptic input Awareness of sensations, Motor control. • Cerebellum Balance, Muscle tone, Coordination of voluntary muscle act. Integrative function of the CNS Component Mayor Functions • Brainstem Origin of most cranial nerves, Control center for regulation of cardiovascular, respiratory, and digestive systems. Regulation of muscle reflexes for posture and equilibrium. Integration of all synaptic input from spinal cord. • Hypothalamus Homeostatic regulation of temperature, thirst, food intake, fluid balance, and biological rhythms. Relay station between nervous and endocrine systems. Sex drive and sexual behavior Emotions and behavior patterns Sleep–awake cycle. Peripheral Nervous System • Divided into autonomic/enteric and somatic. Somatic NS Consists of nerves connected to sensory receptors and skeletal muscles Permits voluntary action (writing your name) Autonomic NS Permits the Involuntary functions of blood vessels, Glands and internal organs (bladder stomach, lungs and heart…). Peripheral Nervous System • Handles the CNS’s input and output. • Contains all the portions of the CNS outside the brain and spinal cord. • Contains sensory nerves and motor nerves. Sensory Nerves (to the brain) Carry messages from receptors in the skin, muscles, and other internal and external sense organs to the spinal cord and then to the brain. Motor Nerves (from the brain) Carry orders from CNS to muscles/glands to contract and produce chemical messengers. Somatic vs. Autonomic • The efferent nerves of the involuntary system supply all structures of the body except skeletal muscle, which is served by somatic nerves. • The presence of an Autonomic Ganglion (cluster of nerve cell bodies). Somatic nervous system Autonomic nervous system Voluntary muscle Cardiac muscle glands, smooth muscle Adjustment to external environment Adjustment within internal environment Numbers of neurons 1 2 Ganglia outside the CNS ------------ Paravertebral or terminal ganglia Neurotransmitter Acetylcholine Acetylcholine, Epinephrine, Norepinephrine Characteristic Effectors General functions The ANS is most important in two situations: 1- Emergencies that cause stress and require us to "fight" or take "flight" (run away). 2- No emergencies that allow us to "rest" and "digest". Autonomic Nervous System (ANS) • Activities are not under direct conscious control. ✓Visceral (necessary for life) functions such as cardiac output, blood flow distribution, and digestion. • Functions can be divided into three main categories: 1. Homeostasis: provides regulation of the internal environment. 2. Coordinates response to stress and exercise. 3. Assist the endocrine and reproductive systems. • Acts by releasing endocrine hormones or neurotransmitters locally and systemically. • Three main divisions: Sympathetic, Parasympathetic and Enteric. Autonomic Nervous System (ANS) • There are two different types of autonomic fibers interacting with effector organs: 1. Parasympathetic: “rest and digest”; “feed and breed”; energy conservation, rest, grow, reproduce. 2. Sympathetic: “fight or flight”. • The effects of the para- and the sympathetic nervous system are antagonistic. ✓Response depends on the balance between the two systems. ✓Four exceptions that are only innervated by the sympathetic nervous system: 1. 2. Sweat glands. Blood Vessels. 3. Suprarenal glands (adrenal medulla). 4. Pilomotor muscles Afferent fibers Information on the status of the visceral organs is transmitted to the CNS through two main sensory systems: • The cranial or vagus nerve (parasympathetic). ✓The cranial sensory system carries mainly mechanoreceptor and chemosensory information. • The spinal nerve (sympathetic). ✓The spinal sensory system convey sensations related to temperature and tissue injury of mechanical, chemical, or thermal origin. Efferent fibers The efferent side of the ANS consists of motor neurons. The efferent ANS has two large divisions: • The cranial or vagus nerve (parasympathetic). • The spinal nerve (sympathetic). • Both Parasympathetic and Sympathetic efferent fibers innervate the same effectors, and the response depends on the balance between them. General functions of the ANS • ANS the primary regulator of the constancy of the internal environment of the organism. ✓Functions below the level of consciousness. Controls respiration, circulation, digestion, body temperature, metabolism, sweating, and the secretions of certain endocrine glands. • The parasympathetic system ✓Concerned primarily with conservation of energy and maintenance of organ function during periods of minimal activity. ✓Organized mainly for discrete and localized discharge. General functions of the ANS The Sympathetic system: • Prepares the organism for a "fight or flight” response. • The sympathetic system and its associated adrenal medulla are not essential for life (controlled environment), but its importance becomes evident under circumstances of stress. ✓Body temperature cannot be regulated when environmental temperature varies; the concentration of glucose in blood does not rise in response to urgent need; compensatory vascular responses to hemorrhage, oxygen deprivation, excitement, and exercise are lacking. Sympathetic system • Responsible for “fight or flight” response: ✓Mydriasis ✓Positive Ino- and chronotropic effect on the heart. ✓Arterial vasodilation. ✓Bronchi s. muscle dilation. ✓↓ digestion and urine formation. ✓↑ glycogenolysis. Sympathetic system • Preganglionic fibers of this division lie in the intermediolateral columns of the spinal cord. The axons from these cells are carried in the anterior (ventral) nerve roots and synapse, with neurons lying in sympathetic ganglia outside the cerebrospinal axis. • Sympathetic mainly: ✓Paravertebral. ganglia are found Sympathetic system • Thoracolumbar, most sympathetic preganglionic fibers are short and terminate in ganglia located in the paravertebral chains that lie on either side of the spinal column. Anatomical characteristics of the sympathetic divisions Adrenal Medulla • The adrenal medulla resembles embryologically and anatomically sympathetic ganglia. ✓Differs from sympathetic ganglia in that its principal catecholamine is epinephrine (adrenaline) not norepinephrine. • The chromaffin cells in the adrenal medulla are innervated by typical preganglionic sympathetic fibers that release ACh. • The adrenal medulla release epinephrine into the bloodstream in stress situations. The Adrenal Medulla • Major organ of the sympathetic nervous system. • Secretes great quantities of epinephrine (a little norepinephrine). • Stimulated to secrete by preganglionic sympathetic fibers. Hypothalamus activates Fig. 45.34(TE Art) sympathetic division of nervous system Heart rate, blood pressure, and respiration increase Adrenal medulla secretes epinephrine and norepinephrine Blood flow to skeletal muscles increases Stomach contractions are inhibited Similarities between sympathetic and parasympathetic • Both are efferent (motor) systems: “visceromotor”. • Both involve regulation of the “internal” environment outside of our conscious control: “autonomous”. • Both involve 2 neurons that synapse in a peripheral ganglion and innervate glands, smooth muscle and cardiac muscle. glands CNS ganglion smooth muscle preganglionic neuron postganglionic neuron cardiac muscle Parasympathetic • Responsible for “rest and digest” or "feed and breed” response: ✓Miosis. ✓Negative inotropic and chronotropic heart effects. ✓Bronchi s. muscle constriction. ✓↑ saliva and urine production. ✓↑ digestion and defecation. . Parasympathetic System • Preganglionic fibers originate in the CNS. • The vagus nerve has widest distribution of ANS and is responsible more than 75% of parasympathetic activity. the the for the • Parasympthetic ganglia are located in close proximity to the effector organ. Anatomical characteristics of parasympathetic divisions Differences between Sympathetic and Parasympathetic Location of Preganglionic Cell Bodies Sympathetic Parasympathetic Thoracolumbar Craniosacral T1 – L2/L3 levels of the spinal cord Brain: CN III, VII, IX, X Spinal cord: S2 – S4 Differences between Sympathetic and Parasympathetic Relative Lengths of Neurons Sympathetic CNS target ganglion short preganglionic neuron long postganglionic neuron Parasympathetic ganglion CNS long preganglionic neuron target short postganglionic neuron Differences between Sympathetic and Parasympathetic Neurotransmitters Sympathetic NE (ACh at sweat glands) + / - α & ß receptors ACh + Parasympathetic ACh + / - ACh + muscarinic receptors • All preganglionics release acetylcholine (ACh) & are excitatory (+) • Postganglionic ✓Parasympathetic ACh excitatory (+) or inhibitory (-). ✓Sympathetic NE & are excitatory (+) or inhibitory (-). Excitation or inhibition is receptor-dependent. Sympathetic N.S. Like the accelerator of your car Parasympathetic N.S. Like the brakes in your car Slows the body down to keep its rhythm Mobilized the body for action Enables the body to conserve and store energy Preganglionic: short, synapse within the lateral & collateral ganglia Preganglionic: long, synapse within the terminal ganglia Postganglionic: long Postganglionic: short Has a wide distributions Has a restricted distributions • Often work in opposition. Autonomic Nervous System • Cooperate to finetune homeostasis. • Regulated by the brain; hypothalamus. • Can also be regulated by spinal reflexes; no higher order input. • Pathways both consist of a twoneuron system. Preganglionic neuron from CNS autonomic ganglion outside CNS postganglionic neuron target Carotid and aortic arteries Cardiovascular System ANS integration Enteric Nervous System • The ENS is a large and highly organized collection of neurons located in the walls of the gastrointestinal (GI) system. It is considered a third division of the ANS. • Controls the processes of mixing, propulsion, and absorption of nutrients in the GI tract. • The ENS is involved in sensorimotor control and thus consists of both afferent sensory neurons and a number of motor nerves. Enteric Nervous System • Involved in both motor and secretory activities of the gut. • It is particularly critical in the motor activity of the colon. The ENS includes the myenteric plexus (the plexus of Auerbach) and the submucous plexus (the plexus of Meissner). Neurotransmiters of the ANS • All preganglionic neurons of the ANS are cholinergic (release acetylcholine [ACh]). ✓Interact with nicotinic acetylcholine receptors postganglionic fibers. in • Postganglionic neurons of the parasympathetic nervous system are also cholinergic. ✓Muscarinic receptors. • Postganglionic neurons of the sympathetic nervous system are adrenergic (release NE or epinephrine in the case of the adrenal medulla). ✓Adrenergic receptors Neurotransmission • Transmission of information in the nervous system, from chemical to electrical that occurs between nerve cells and between nerve cells and their effector cells. • By using drugs that mimic or block the actions of chemical transmitters, we can selectively modify many autonomic functions. ✓Autonomic drugs are useful in many clinical conditions. Unfortunately, a very large number of drugs used for other purposes have unwanted effects on autonomic function. Neurotransmission 1. Axonal conduction ✓Activation of voltage gated channels causes depolarization which results in neurotransmitter release. 2. Junctional transmission ✓Neurotransmitter with receptors synaptic cleft. interact at the ✓ Response is stopped by 1. Diffusion 2. Reuptake 3. Enzymatic breakdown Neurotransmitter Synapse 3D Animation - Copy.mp4 Postsynaptic Potentials EPSP: Excitatory Postsynaptic Potentials IPSP: Inhibitory Postsynaptic Potentials Types of Receptors Ligand gated ion channels Nicotinic Acetylcholine Receptors • Ionotropic: receptor and ion channel at the same time, do not use second messengers. • Activated by ACh or nicotine. • Produce excitation 1. Neuronal nicotinic (NN): autonomic ganglia of the sympathetic and parasympathetic nervous system. 2. Muscle nicotinic (NM): neuromuscular junction. Types of Receptors Ligand gated ion channels Nicotinic Acetylcholine Receptors Cations ACh Cellular events Figure 8-2 Types of Receptors G-protein coupled receptors Adrenergic Receptors Muscarinic Receptors Outside Outside Ligand Effector Inside Inside Effector GPCR γ GDP GTP β Gα Heterotrimeric G-proteins : Gαs, Gαi/o, Gαq/11, and Gα12/13 Types of G proteins Main G-proteins Actions • Gs ✓Activates Na+ channels ✓↑ adenylate cyclase activity • ↑cAMP • Gi/o ✓Activates K+ channels ✓Inhibits Ca+2 channels ✓↓ adenylate cyclase activity • ↓cAMP • Gq ✓Activates phospholipase C • ↑ Intracellular Calcium Types of Receptors GPCR Muscarinic Receptors • M1: ganglion and exocrine glands (excitatory, Gq) ✓Mediates slow EPSP in autonomic ganglia. ✓Secretion from the salivary glands and from stomach (gastric acid). • M2: ganglion and heart (inhibitory, Gi). ✓Mediates IPSP in autonomic ganglia. ✓Negative inotropy and chronotropy. • M3: smooth muscle, lungs, pancreas and exocrine glands (excitatory, Gq). ✓↑ smooth muscle contraction (GI motility). ✓↑ glandular secretions. ✓Critical regulators of glucose homeostasis by modulating insulin secretion. Types of Receptors GPCR Muscarinic Receptors • M4: CNS and PNC (vagus nerve)(inhibitory, Gi). ✓Autoreceptor (presynaptic receptor that serves as a feedback mechanism for further neurotransmitter release). ✓Heteroreceptor (controls the release of neurotransmitter by other neurons), inhibitory in SNS. • M5:CNS (excitatory, Gq). Types of Receptors GPCR Muscarinic Receptors Types of Receptors GPCR Adrenergic Receptors 1. Alpha 1 Receptors (a1ARs): Vascular smooth muscle, GI, bladder sphincter and muscle of the iris (excitatory, Gq). ✓Smooth muscle contraction (vasoconstriction). 2. Alpha 2 Receptors (a2AR): presynaptic nerve terminals, platelets, fat cells and GI tract (inhibitory, Gi). ✓Produces relaxation or dilation by inhibiting the release of norepinephrine (autoreceptor negative feedback). Types of Receptors GPCR Adrenergic Receptors 1. Beta 1 Receptors (b1AR): heart (SA and AV nodes and ventricular muscle)(excitatory, Gs). ✓Positive inotropy and chronotropy. ✓Smooth muscle contraction (vasoconstriction). 2. Beta 2 Receptors (b2AR): smooth muscle (vascular, bronchial, GI tract and bladder)(excitatory, Gs). ✓Relaxation of smooth muscle (↓ GI motility, dilation of bronchi passage). 3. Beta 3 Receptors (b3AR): adipocytes (excitatory, Gs). ✓Mediates lipolysis in adipocytes. Types of Receptors GPCR Adrenergic Receptors Vasoconstriction Presynaptic: Suppression of release of norepinephrine by negative feedback. Postsynaptic: smooth muscle contraction b1ARs: Heart muscle contraction b2AR: Smooth muscle relaxation b3AR: Lypolisis