Physiology 1.03 - Neurophysiology-ANS

1.03

PHYSIOLOGY NEUROPHYSIOLOGY: AUTONOMIC NERVOUS SYSTEM

JULY 2, 2013

Katherine Munarriz, M.D. NERVOUS SYSTEM

that all of the sensory stimuli that have been integrated are brought to the PFC for analysis)

Two major types: CNS and PNS CNS: consist of brain and spinal cord but also retina innervated by cranial nerve II optic nerve *Cranial nerves are part of peripheral nervous system except for cranial nerve II Multiple sclerosis: Cranial nervous system affected  patients have optic problems (optic nerve involvement) PNS: cranial and spinal nerves (originate at brainstem and spinal cord then go to the periphery) 2 Parts: Somatic and Autonomic Nerves (Sympathetic, Parasympathetic and Enteric)  Autonomic - supply cardiac or smooth muscles and glands in subconscious control  Somatic - conscious control over skeletal muscles ORGANIZATION OF CNS Forebrain: Cerebral hemispheres (left and right); Diencephalon Brainstem: midbrain and hindbrain (pons and medulla) Spinal Cord

PFC analyzes every sensory stimulus that you have to incorporate in your decision to become a doctor. All of the sensory information not only from the cerebral cortex, but even from the limbic lobe which is in the medial portion of the cerebral hemispheres or the diencephalon. Why is the PFC in the motor lobe? Basically because the PFC which has decided is also the one making you go to PLM every day. Without which you will not be able to diagnose your patient. Incorporating all of the sensory information from your patient, all of that have to be analyzed by the PFC including what you know in your temporal lobes about diseases. Limbic lobe is another association area that will help the PFC to decide. What is being analyzed here are all your emotional responses to all the stimuli ever since you were in your mother’s womb. More than your cortical analysis is your subcortical analysis that is the greater reason why you are here.

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Organization of Cerebral Hemispheres Frontal Lobe: Motor Parietal Lobe: Areas 3,1,2 (Primary Somatosensory Area) Occipital lobe: Visual (Sensory) Area 17: Primary Visual center Area 41: Primary Auditory center Area 4: Primary motor area Area 6: Secondary motor area (Pre-motor area) Medial portion – Supplementary motor area Rest of frontal lobe – Pre-Frontal Cortex (association area that takes into consideration inputs from the sensory association areas, so

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BRAINSTEM made up of midbrain, pons and medulla divided into 3 parts: tectum from tegmentum; at the base you have motor tracts (corticospinal tract which originate from motor cortexes and pass to spinal cord, and corticobulbar tract, CBT, are the upper motor neurons of the cranial nerves supplying skeletal muscles of face and neck) Base is made up of motor tracts; near the canal are cranial nerve nuclei. At the tegmentum are additional motor tracts, cranial nerves 3 & 4 in the midbrain. In the pons cranial nerves 5, 6, 7, & 8 (large – both tectum and tegmentum). In the medulla, cranial

PHYSIOLOGY

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NEUROPHYSIOLOGY: ANS

nerves 9, 10, 11 & 12. Cranial nerves that arise near the canal are cranial nerves 3, 6 & 12. Exceptions are cranial nerve 8 which can be found in the lower pons and upper medulla and cranial nerve 5 which will encompass whole brainstem, even up to cervical spinal cord.

Cranial Nerve Functions - General Sensory Afferents (GSA) are cranial nerves 5, 9 & 10. General sensations do not include taste, only tactile, proprioceptive, etc. Review: CN 1 – S CN 2 – S CN 3 – M CN 4 – M CN 5 – BOTH CN 6 – M CN 7 – BOTH CN 8 – S CN 9 – BOTH CN 10 – BOTH CN 11 – M CN 12 – M - Special Senses are cranial nerves 2 & 8; special visceral afferents are smell and taste. - General Visceral Afferents are 9 & 10 - Somatic striated muscles are 3, 4 & 6 - Branchial arch striated muscles are separated from 3, 4 & 6 in that they are bilaterally innervated. For example, CN 7 facial nerve (LMN). If we lesion CN 7? Both upper and lower facial muscles will be affected  Bell’s palsy is when the entire half of the facial muscle is affected. The lesion is ipsilateral (same side). If we lesion upper motor neuron CBT specifically affecting CN 7? Since upper motor neurons are bilateral, only the lower facial muscle of the opposite side will be affected, therefore patient can frown and do all of the upper facial muscle

actions. The patient will have contralateral lower facial paralysis. *Both CST and CBT decussate (cross over) before synapsing with the lower motor neuron. REFLEX REFLEX ARC- basic unit of integrated activity Reflex Arc - 5 anatomic components and 2 physiologic components - First is the stimulus, receptor, afferent nerve (pass thru the center whether spinal cord or brainstem), then synapse with efferent nerve (supply impulses to agonist muscles) and response. - Monosynaptic reflex arc: only one synapse - Polysynaptic reflex Components of the reflex arc - Stimuli - Receptor- the sense organ - Afferent neuron- enters via dorsal roots or cranial nerves - Center- center of integrating stations, may be the brain or spinal cord - Efferent neuron- leaves via ventral roots or corresponding cranial nerves - Effector organs- the muscle/organ that would respond to the stimulus - Response DYNAMIC STRETCH REFLEX -

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only reflex that will display monosynaptic reflex arc Ia afferent will synapse with alpha motor neuron, only monosynaptic reflex found in humans. But there is also gamma motor neuron, not monosynaptically connected with Ia. Ia will connect with alpha motor neuron and excitatory interneurons that will Page 2 of 18

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PHYSIOLOGY

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NEUROPHYSIOLOGY: ANS

synapse with gamma motor neurons. Entire dynamic stretch is both monoand polysynaptic. But in board exams, what is the only monosynaptic reflex? DYNAMIC STRETCH. Interneurons abound in the spinal cord and brainstem. If excitatory then it will continue the relay of impulses. If inhibitory then it will not allow conveyance of impulses to specific nerve. Table of dynamic stretch reflex  Stimulus: Sudden rapid stretch of muscle spindle, not the tendon. Why? In the lecture about spasticity, you need this and not the tap on the tendon to regenerate the reflex. Motor tracts > Anterior horn cells (alpha-MN and gamma-MN)  Alpha-MN >Extrafusal (nuclear chain fiber)  Gamma-MN >Intrafusal> innervate muscle spindle > dynamic gammaMN contracting nuclear bag fibers and static gamma-MN contracting nuclear chain fibers

Components STIMULUS RECEPTOR AFFERENTS CENTER EFFERENTS EFFECTORS RESPONSE

CORTICOSPINAL TRACT - Inhibitory to reflex > synapse to alpha and gamma MN > inhibit alpha and gamma MN > reflex arc stops - Found in the anterior horn of spinal cord - Originate in cerebrum cortex, end in motor neuron

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Sensory part: Ia afferent will convey impulses, once muscle spindle is stretched, to dorsal horn of spinal cord and synapse with alpha-MN (monosynaptically) and gamma-MN (polysynaptically) > contraction Contractile portion will shorten and noncontractile portion will stretch resulting to rapid stretch of muscle spindle. It is a never-ending, self-perpetuating reflex, unless there were inhibitory mechanisms like the Corticospinal Tract (CST). If there is defective CST there will be spasticity, defined by Guyton as an exaggerated stretch reflex. Beginnings of spasticity will be 3 – 4 months later. Example of hypertonia, because it is as if you are giving the muscle increased tone.

DYNAMIC STRETCH Sudden rapid stretch of muscle spindles Muscle spindle Ia afferents of femoral nerve L2-L4 Femoral nerve Knee extensor muscle (quadriceps femoris) Contraction of extensors (knee extension)

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INVERSE STRETCH REFLEX Second inhibitory mechanism for preventing muscle spasticity Stimulus: Increased tension in the quads or a tap in the tendon > Golgi tendon organs >Ib afferent Inhibitory interneuron > inhibits motor neuron going to agonist muscle while exciting motor neuron going to antagonist muscle Response: Knee flexion, decreased tension in the quads, cessation of stretch reflex

Components STIMULUS RECEPTOR AFFERENTS CENTER EFFERENTS

INVERSE STRETCH REFLEX Passive stretch and active contraction of the muscle Golgi tendon organ (GTO) Ib afferent of femoral nerve L2-L4 Femoral nerve Page 3 of 18

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PHYSIOLOGY EFFECTORS RESPONSE

NEUROPHYSIOLOGY: ANS

Flexor muscles (hamstring) Contraction of flexor muscle (knee flexion)

RENSHAW CELL INHIBITORY SYSTEM - Located at the anterior horns of spinal cord - Inhibitory interneurons found in the spinal cord - Some will be synapsing with alpha-MN, and inhibit the same alpha-MN or other alpha-MN hence action potential will not be generated

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FLEXOR WITHDRAWAL REFLEX Seen in lower extremities, especially if you have a painful stimulus applied to the feet > cause entire lower extremity to withdraw > painful stimulus will activate free nerve endings feet > affect A, delta and C afferents of the medial plantar nerve > L4 cord level (L4 – S2) > synapsing with agonists and antagonists > inhibiting agonists and facilitating antagonists (knee flexors, ankle dorsiflexors, hip flexors) Triple flexion response: Hip flexion, Knee flexion, and Ankle dorsiflexion  lifting of the entire leg upwards other leg will extend (Cross extensor reflex) Not usually seen in upper extremities  Triple flexion response include finger flexion, elbow flexion and shoulder flexion

Components STIMULUS RECEPTOR AFFERENTS CENTER EFFERENTS EFFECTORS

FLEXOR WITHDRAWAL REFLEX Hot plate/ painful stimulus Pain receptors A delta and C afferentsof cutaneous nerve L2-L4 Femoral nerve Flexor muscles

RESPONSE

Contraction of flexor muscles ( Triple flexion response of the lower extremities)

CROSSED EXTENSION REFLEX - Brought about by flexion withdrawal reflex - Extension of the contralateral leg RECIPROCAL INHIBITION - If a muscle is facilitated or excited, the other one will be inhibited (antagonist). - Example: knee jerk, Inverse stretch reflex Somatic reflexes (LMN) and cerebral congnition of those reflexes so you will know when you’re limb is still or when you’re limb already jerked.

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AUTONOMIC REFLEXES Long reflexes and short reflexes ANS neurons: pre-ganglionic and postganglionic

SNS vs PSNS – regulation of final effect In the midbrain, you will find Cranial Nerve 3 which is a parasympathetic nerve that will affect pupilloconstrictor muscles. (Activate PSNS, pupilloconstriction. Activate SNS, pupillodilation.) In the midbrain, there are SNS descending fibers from hypothalamus such that if there is a lesion in midbrain, both SNS and PSNS are affected. The eye will be in a fixed position when you pass a pen light, neither dilating nor contracting (fixed mid position). If only cranial nerve 3 is affected or has lesion then the pupil will be dilated. If there is a lesion in the lateral part of the brainstem, myosis or abnormal pupilloconstriction.

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PHYSIOLOGY

NEUROPHYSIOLOGY: ANS

ORGANIZATION OF SPINAL CORD -

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Dorsal and ventral side (motor neuron) Lamina 8 & 9 (Motor) that house alphaand gamma-MN Lamina 1 -6 (Sensory) belong to dorsal horn of gray matter of spinal cord, thru these will pass the sensory nerves Lamina 7 (Sensory) – Clarks nucleus and intermedio lateral horn > form lateral part of the gray matter of spinal cord *Spinocerebellar tracts Origin of Autonomic Nervous System: Intermedio lateral horn Origin of SNS fibers: T1 – L2 Origin of PSNS fibers: S2 – S4 Lamina 10 (Motor) – surrounding central canal, thru it will pass Spinothalamic tract

SYMPATHETIC NERVOUS SYSTEM One of the main divisions of the Autonomic Nervous System (ANS) - Relays the body’s responses to stress (Fight or flight response) - It is an example of an efferent motor system -

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o Spinal nerve o White ramus (Myelinated) o Sympathetic chain At the sympathetic chain level, the fibers pass through any one of these paths: o Synapse with postganglionic sympathetic neurons in the paravertebral ganglion then travel to viscus organs. o Synapse with postganglionic sympathetic neurons in the paravertebral ganglion and pass through the gray ramus then travels to blood vessels and sweat glands o Pass through a sympathetic nerve and synapse with prevertebral ganglion (peripheral or collateral ganglion) then travel to viscus organs The primary neurotransmitter released at the synapses is Acetycholine (Ach)= cholinergic neurons

Parts of the SNS Spinal cord origins - The SNS nerve fibers originate from the spinal cord between the spinal cord segments T1 and L2 - There are two parts of the sympathetic pathway: preganglionic and postganglionic Preganglionic part - Cell bodies are found in the intermediolateral horn - Fibers from the intermediolateral horn passes through: o Anterior or motor root of spinal cord Page 5 of 18

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PHYSIOLOGY

Path 1: Intermediolateral horn→Anterior root → Spinal nerve → White ramus → Paravertebral ganglion → Postganglionic neuron→Viscus organ Path 2: Intermediolateral horn → Anterior root → Spinal nerve → White ramus → Paravertebral ganglion → Postganglionic neuron → Gray ramus→Blood vessels, sweat glands

NEUROPHYSIOLOGY: ANS

Neurotransmitters involved in SNS: Neurotransmitter Receptor SNS Epinephrine, (Adrenergic) Norepinephrine α1, α2 β1, β2 PSNS

Acetylcholine

(Cholinergic) Nicotinic Muscarinic

Path 3: Intermediolateral horn →Anterior root → Spinal nerve → White ramus → Sympathetic nerve →Prevertebral ganglion → Postganglionic neuron →Viscus organ Paravertebral ganglia- bilateral, forms the sympathetic chain of synapse locations Prevertebral ganglia: 1. Celiac (CG) 2. Superior mesenteric (SMG) 3. Inferior mesenteric (IMG) Postganglionic - At the synapse, the postganglionic neurons contain nicotinic receptors - These receptors receive the Ach from the preganglionic neurons - Action potentials flow from the synapse to the axon terminal at the effector organ - The axon terminal of the postganglionic neuron secretes norepinephrine (adrenergic) as its primary neurotransmitter - However, neurons directed to blood vessels and sweat glands release Ach (cholinergic) - Norepinephrine is received by adrenergic receptors while Ach is received by muscarinic receptors

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Norepinephrine is released by the axon terminal 80% of the time The other 20% is comprised of epinephrine SYNTHESIS AND SECRETION OF NEUROTRANSMITTERS Neurotransmitters are synthesized in bulbous areas of the neuron called varicosities

Release of neurotransmitters: Action potentials → Increased permeability of fiber membrane to Ca++ ions →Ca++ influx in axon terminal/varicosities →vesicles attach to Page 6 of 18

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PHYSIOLOGY membrane via SNARE action → exocytosis of neurotransmitter Acetylcholine

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After its action, the Ach molecule splits into acetate ion and choline, catalyzed by acetycholinesterase Choline will be transported back to nerve fiber and will be recycled

Norepinephrine

NEUROPHYSIOLOGY: ANS transferase (COMT) in the postsynaptic cell 2. Reuptake by alpha 2 receptors in the membrane of the axon terminal 3. Diffusion away from the nerve endings and into surrounding body fluids = loss of function Effects of drugs on the action of norepinephrine (NE) removal: - MAO inhibitor:↑ effect of NE - Reserpine: ↓ effect due to inhibition of NE incorporation to vesicles - Alpha 2 agonist: ↓ effect due to increased reuptake of NE - Beta blockers: ↓ due to reduced sensitivity of postsynaptic receptors - Alpha blockers: ↓(same as beta)

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Synthesis: 1. Hydroxylation of Tyrosine to DOPA 2. Decarboxylation of DOPA to Dopamine 3. Dopamine is transported to vesicles 4. Hydroxylation of Dopamine to Norepinephrine Removal of Norepinephrine 1. Degradation by monoamine oxidase (MAO) in the cytosol of the axon terminal and by catechol o-methyl

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RECEPTORS OF SNS These are found in the postsynaptic membrane of either the postganglionic neuron or the effector organ Binding of a neurotransmitter to a receptor elicits several responses: o Excitation or inhibition of the cell. This is done by opening/closing certain ion channels. (Na and Ca influx=excitation; K efflux=inhibition) o Activating/inactivating secondary messengers e.g. cAMP, IP3, etc. There are two types in the SNS: cholinergic and adrenergic

Cholinergic receptors - Has two types: Nicotinic and Muscarinic Nicotinic - Stimulated by nicotine - Found in the autonomic ganglia of both PSNS and SNS (in the postganglionic neuron) Page 7 of 18

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PHYSIOLOGY -

NEUROPHYSIOLOGY: ANS

Ligand gated, non-selective cation channel When activated by Ach induces an influx of Na+ and movement of K+ → depolarization of neuron

Muscarinic - Stimulated by Muscarine - Found in the effector cells of both PSNS and SNS (primarily on PSNS; in SNS, found in blood vessels and sweat glands) - Effect lies on the activation of G protein complex (Secondary messenger system) Adrenergic receptors - Has two main types, alpha and beta receptors Alpha receptors - Has two types: alpha 1 and alpha 2 - Excited primarily by Norepinephrine - Found in various organs such as smooth and cardiac muscles - Alpha 1 o Is found in primarily on postsynaptic terminals (effector) o When activated, causes smooth muscle contraction o GPCR activates PLC → conversion of PIP to IP3 → Ca2+ release from SR → SmM contraction o Found mostly in smooth muscles

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Alpha 2 o Is found on presynaptic axon terminals o Functions in the regulation of norepinephrine concentrations o Also functions in Vasoconstriction o Blood vessel SmM → reduced action potential → reduced cAMP → SERCA does not pump → less reuptake of Ca2+ → more Ca2= available → vasoconstriction

Beta receptors - Excited mainly by Epinephrine - Has three types: beta 1, beta 2, and beta 3 - Beta 1 o Primary receptor in cardiac muscle o Causes cardiac muscle contraction o Myocardium → ↑ cAMP → phosphorylation of sarcolemmal Ca2+ channel → Ca2+ influx → contraction of cardiac muscle

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PHYSIOLOGY

NEUROPHYSIOLOGY: ANS receptors, but it also has beta 2 receptors which are deemed insignificant. *Epinephrine- more significant for Beta receptors *Norepinephrine- more significant for Alpha receptors

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Beta 2 o Present in smooth muscle o Causes smooth muscle relaxation o GIT, SmM of GUT, pulmonary bronchioles →↑ cAMP phosphorylates SERCA →Ca2+ pumped back into SR → Relaxation

Adrenergic Receptors Alpha Receptor Beta Receptor Vasoconstriction Vasodilation (β2) Iris dilation Cardioacceleration (β1) Intestinal relaxation Increased myocardial strength (β1) Intestinal sphincter Intestinal relaxation contraction (β2) Uterus relaxation (β2) Pilomotor contraction Bronchodilation (β2) Bladder sphincter Calorigenesis (β2) contraction Inhibits Glycogenolysis (β2) neurotransmitter Lipolysis (β1) release (α2) Bladder wall relaxation (β2) Thermogenesis (β3) Again to summarize… Alpha 1- ↑ IP3 for contraction Alpha 2- ↓ cAMP Beta 1- ↑ cAMP Beta 2- ↑ cAMP

*The functions, actions of the organs are highly dependent on the type of receptors it has. For example, the heart primarily contains beta 1

Epinephrine vs Norepinephrine Epinephrine Norepinephrine % amount 20% 80% released from neurons % amount 80% 20% released from adrenal medulla Receptor Primarily Primarily alpha targets beta Page 9 of 18

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PHYSIOLOGY Cardiac stimulation

Beta 1 receptors in the myocardium → increased cardiac output →increased BP

NEUROPHYSIOLOGY: ANS Alpha receptors in blood vessels →vasoconstriction →increased BP

5. Increased glycolysis in the liver and in muscle 6. Increased muscle strength 7. Increased mental activity 8. Increased rate of blood coagulation -

Phenomenon is basis for fight or flight response

Higher influence on ANS control *Epinephrine increases cardiac output (CO) → increased blood pressure *Norepinephrine increases total peripheral resistance (TPR) through vasoconstriction → increased blood pressure *Epinephrine also increases metabolic rates dramatically, compared to Norepinephrine which has minimal effects - Beta receptors (b2 in liver, muscle; b3 in adipose → increased cAMP → pKA → lipolysis (in liver, glycogenolysis) (COMPLETE EFFECTS TABLE IN BERNE AND LEVY) Mass effect or mass discharge - The SNS is capable of affecting several organs during times of stress (systemic) - The PSNS only have localized effects - Mass discharge occurs when the hypothalamus is activated by fright or fear/pain - This is the reaction of the SNS during extreme, sudden stress Effects of mass discharge 1. Increased arterial pressure 2. Increased blood flow to active muscles concurrent with decreased blood flow to organs such as the gastrointestinal tract and the kidneys that are not needed for rapid motor activity 3. Increased rates of cellular metabolism throughout the body 4. Increased blood glucose concentration

1. Limbic Lobe (Amygdala) 2. Hypothalamus (Overall integration of ANS) - Posterior hypothalamus is for sympathetic functions - Anterior hypothalamic: thermoregulation - Paraventricular: Corticoreleasing hormone →Adreno-cortico releasing hormone→ cortisol 3. Reticular formation/ Reticular activation system (RAS) PARASYMPATHETIC NERVOUS SYSTEM  Leave the CNS through CN III, VII, IX, and X  Leave the lower SC through 2nd and 3rd sacral nerves, occasionally, the 1st and 4th  75% of PS nerve fibers are in the vagus nerves (CN X) which supply PS nerve fibers to the heart, lungs, esophagus, stomach, entire small intestine, proximal half of the colon, liver, gall bladder, pancreas, kidneys, and upper portion of the ureters  Referred to as craniosacral division

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PHYSIOLOGY

NEUROPHYSIOLOGY: ANS Mechanisms of Transmitter Secretion and Subsequent Removal of the Transmitter at Postganglionic Endings 

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 Preganglionic and Postganglionic Parasympathetic Neurons 

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Except in the case of a few cranial PS nerves, preganglionic fibers pass uninterrupted all the way to the organ to be controlled The preganglionic neurons synapse with the postganglionic neurons found in the walls of the organs Preganglionic neurons are cholinergic, as are the postganglionic neurons but there are some exceptions - PS nerve fibers to the: sweat glands, piloerector muscles of the hairs, and a few blood vessels (adrenergic)

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Varicosities – bulbous enlargements where the vesicles of acetylcholine and norepinephrine are synthesized; touch or pass by organs or connective tissues of the organs innervated AP spreads over fiber terminal Depolarization Increased permeability of membrane to Ca2+ Ca2+cause the terminals or varicosities to empty their contents transmitter substance is secreted ACh synthesis: Acetyl-CoA + Choline –choline acetyltransferase Acetylcholine ACh remains only for a few seconds following secretion, after which it is split into acetyl ion and choline by acetylcholinesterase The choline that is formed is then transported back into the terminal nerve ending to be used again for ACh synthesis

Receptors on the Effector Organ 

Binding of neurotransmitter with the receptors alters the protein molecule which in turn excites or inhibits the cell via: a) causing a change in cell membrane permeability to one or more ions e.g. excitation via opening the Ca2+ and Na+ channel and inhibition via opening the K+ channel Page 11 of 18

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PHYSIOLOGY

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b) activating or inactivating an enzyme attached to the other end of the receptor protein e.g. binding of norepinephrine increases adenylyl cyclase activity Two principal types of ACh receptors: a) Muscarinic – found on all effector cells stimulated by postganglionic neurons of either SNS or PSNS o M3 – found in smooth muscles and glands o M2 – found in the heart o M1, M3, M5 – excitatory o M2, M4 - inhibitory b) Nicotinic – found in the autonomic ganglia at the synapses between the preganglionic and postganglionic of both SNS and PSNS; also present at nonautonomic nerve endings, e.g. NMJ in skeletal muscle

Excitatory and Inhibitory Actions of Parasympathetic Stimulation 

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Both sympathetic and parasympathetic stimulation cause excitatory effects on some organs but inhibitory effect on others. When sympathetic stimulation excites a particular organ, parasympathetic stimulation sometime inhibits it. However, most organs are dominantly controlled by one or the other of the two systems

NEUROPHYSIOLOGY: ANS

Reticular Formation  Bilaterally located in the brainstem in the tegmentum  Nucleus tractus solitarius (NTS) – sensory area which receives input from the CN VII and IX (taste information), heart, lungs, liver, etc. - these inputs will have a motor arc from the NTS going to PS neurons to the said organs, giving out PS responses - increasing PS responses decreases SNS response Baroreceptor Reflex  Baroreceptors -stretch receptors - will fire only aortic arch and carotid sinus are stretched (due to increased blood volumegreater pressure against BV walls) - convey impulse from CN IX (coming from carotid sinus) and X (from aortic arch)  NTS receives the impulse and increase PSNS effects, which then inhibits the vasomotor center thus decreasing SNS firing.  Decrease in SNS firing and increase in PSNS firing is achieved through the preand postganglionic vagal nerve primarily affecting myocardial BV  Increase in blood pressure (BP) gives rise to blood pressure response. BP = CO•TPR CO=SV•HR SV=preload, afterload, and myocardial contractility (MC) MC  SV  HR  CO  BP Page 12 of 18

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PHYSIOLOGY

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NEUROPHYSIOLOGY: ANS

Vasodilation will also decrease TPR, resulting to decreased BP. Firing from baroreceptors caused by increase in blood volume inhibits the pre-frontal cortex (PFC) and excites the dorsal motor nucleus of the vagus nerve until it decreases HR. There is less PSNS effect in the ventricles.

BARORECEPTOR REFLEX STIMULUS INCREASED BP, STRETCH RECEPTOR BARORECEPTORS AFFERENT CN IX (CAROTID SINUS) CN X (AORTIC ARCH CENTER MEDULLA NTS  INHIBIT VMC EFFERENT DECREASED SNS FIRING EFFECTORS MYOCARDIUM, BLOOD VESSELS RESPONSE DECREASED MCDECREASED HR + VASODILATIONDECREASED BP

Hypothalamus  Pre-optic part – functions for the PSNS; gives you a more stable existence; the one that makes you feel more peaceful (decreased BP and HR) -also functions temperature regulation and sweating

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PHYSIOLOGY

NEUROPHYSIOLOGY: ANS

Responses of effector organs to autonomic nerve impulses

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PHYSIOLOGY

NEUROPHYSIOLOGY: ANS

Relaxation of vascular smooth muscle by inhibitory muscarinic receptors by an effect on endothelial cells which produce endothelium-derived relaxing factor (EDRF) which is actually nitric oxide, a gas released when arginine is converted to citrulline. Calmodulin also activates NO synthase. NO relaxes vascular smooth muscle by stimulating guanylate cyclase thus increasing cGMP levels which in turn activates cGMP-dependent PKG. PKG opens Ca2+-activated K+ channels leading to hyperpolarization. Page 15 of 18

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NEUROPHYSIOLOGY: ANS

Sympathetic and Parasympathetic “Tone” 

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Basal rates of PSNS and SNS activity are referred to as parasympathetic and sympathetic tone respectively Value of tone: allows a single nervous system both to increase and decrease the activity of a stimulated organ Examples a) sympathetic tone keeps systemic arterioles constricted to about ½ their diameter; increasing stimulation will cause further constriction while decreasing it causes dilation b) Background tone of parasympathetics in the GIT; removal of PS nerve supply cause serious and prolonged gastric and intestinal atony with resulting blockage of much of the normal GI propulsion and consequent serious constipation (This tone can be decreased by the brain, resulting to decreased GI motility, or increased, resulting to increased GI activity.)

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Pharmacology of the ANS Drugs That Act on Cholinergic Effector Organs 

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Parasympathetic System: Localized Responses 

In contrast to common mass discharge of SNS Examples: a) PS cardiovascular reflexes usually only act on the heart to increase/decrease its beating b) Other PS reflexes cause secretion mainly by the mouth glands or stomach glands

c) Rectal emptying reflex does not affect other part of the bowel to a major extent There is often association between closely allied PS functions Examples a) Salivary and gastric secretion can occur independently, but also simultaneously together with pancreatic juice secretion b) Rectal emptying reflex often initiates urinary bladder emptying reflex and the latter helps initiate rectal emptying resulting in simultaneous emptying

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Parasympathomimetic Drugs (Cholinergic Drugs)  Pilocarpine and methacholine: act directly on muscarinic receptors Drugs that have a PS potentiating effect (Anticholinesterase Drugs)  Neostigmine, pyridostigmine, and ambenonium: inhibit acetylcholinesterase Drugs that block cholinergic activity (Antimuscarinic Drugs)  Atropine, homatropine, and scopolamine: block the action of ACh on muscarinic type of cholinergic effector organs (no effect on nicotine action)

Drugs That Stimulate or Block Sympathetic and Parasympathetic Postganglionic Neurons

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PHYSIOLOGY 

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NEUROPHYSIOLOGY: ANS

Drugs that stimulate autonomic postganglionic neurons - Nicotine: stimulate in the same manner as ACh because these neurons contain nicotinic receptors - Methacholine: have both nicotinic and muscarinic actions - Pilocarpine: only muscarinic action Ganglionic Blocking Drugs - Tetraethyl ammonium ion, hexamethonium ion, and pentolinium: block ACh stimulation of the postganglionic neurons of PSNS and SNS simultaneously; often used for blocking sympathetic activity rather than parasympathetic because their sympathetic blockage effects far overshadow parasympathetic blockage; can especially reduce arterial pressure in hypertensive people but of not much clinical significance because of effects that are difficult to control.

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