730 Neuropatho Exam 2 - Kelly's guide PDF

730 Neuropatho Exam 2: ANS - sensory, motor, special senses If highlighted in red - was red on the lecture If highlighted orange - i highlighted it/felt like it was emphasized in lecture // yellow is for my brain Green and purple are for me to try to emphasize and separate ideas/color code...

730 Neuropatho Exam 2: ANS - sensory, motor, special senses If highlighted in red - was red on the lecture If highlighted orange - i highlighted it/felt like it was emphasized in lecture // yellow is for my brain Green and purple are for me to try to emphasize and separate ideas/color code Lecture One - Somatosensory (we learned a lot of this last semester) ❖ The nervous system Central - brain and spinal cord Peripheral - somatic (motor/voluntary) and autonomic (sympathetic and parasympathetic) ❖ Terms ❖ Types of sensations Mechanoreceptive - touch and pressure Thermoreceptive - temp Nociceptors - pain Exteroceptive - from surface of the body Proprioceptive - position sense Visceral - internal organs Deep sensations - from deep tissue All sensation involves: receptor activation → neuron activation → impulse transmission to the spinal cord and brain ❖ Specialized sensory receptors Mechanoreceptors - mechanical compression or stretching Free nerve endings Expanded tip receptor: sustained touch, texture discrimination Tactile hair: detects movement on surface of body/initial contact with body Pacinian corpuscle: deep vibration, movement against skin, pressure Meissner’s corpuscle: Sensitive to skin touch, low frequency vibration (found on non hairy skin fingertips/lips) Krause’s corpuscle: touch, pressure, temperature Ruffini’s end-organ: deep and prolonged pressure, skin stretch; found in joints Golgi tendon apparatus: proprioception Muscle spindle: proprioception Thermoreceptors - changes in temperature Nociceptors - physical or chemical damage to tissue (pain) Electromagnetic - light on retina of eye Chemoreceptors - taste/smell; O2/CO2 in blood; osmolality, etc. ❖ Neuron activation and transmission Differential sensitivity - “wind vs. touch, hair follicle won’t be affected by pressure since it’s not supposed to detect pressure” Receptors are designed for specific types of stimuli Receptors are almost non-responsive to other types of sensory stimuli Labeled-line principle - “brain recognizes stimulation based on the ‘line’ it comes from” Specificity of nerve fibers to transmit only one modality of sensation Each nerve tract terminates at a specific point in the CNS Type of sensation felt is determined by the specific nerve fiber stimulated “If pain receptor is what is stimulated - you feel pain regardless of what type of stimulus it was that that activated it” ❖ Receptor potentials Stimuli change the electrical membrane potential (receptor potential) → ion channels open “ → electrochemical stimulus → information is sent to the brain” - “this shows how electrolyte abnormalities can affect neural transmission” Mechanisms Mechanical deformation: mechanical pressure causes stretch of the receptor membrane; stretch of membrane opens ion channels Chemical application: chemical application to membrane opens ion channels Temperature change: change in temperature alters permeability of membrane Electromagnetic radiation: light on retina causes ion channels to open ❖ Action potentials Threshold - the potential must rise above a certain threshold to elicit an action potential (all or none response)  Frequency - “the brain should recognize repetitive firing differently” The more the receptor potential rises above the threshold the greater becomes the action potential frequency Very intense stimulation causes progressively less and less additional action potentials Allows range of sensory experience (weak > intense) Amplitude - “the bigger the stimulus → the brain should recognize that it’s bigger” Increases rapidly with increased stimulus strength but progressively less less rapidly at high stimulus strength” In our words/understanding: Frequency - if your pain is a 3/10 pain, your frequency has a lot of room to increase. This “low level” stimulation, as it increases, has a lot of room to increase so it will progressively have more “additional action potentials” once it gets up to a 5 or 7, etc. However, once you’re at a 9/10 the actional potential frequency can only increase so much - aka as it increases in intensity (9/10 or 10/10 pain) the room for “additional action potentials” becomes less Amplitude - the height between -70 mV and +30 mV is much higher than -30 and +30 So an initial increased stimulus has a high amplitude, but if the stimulus is intense the amplitude will continue to decrease as the frequency increases Both have big changes initially, but both the space between/frequency of additional action potentials and the amplitude/height of response to change decrease Test question from last semester: In pacinian corpuscles (touch, vibration, rapidly adapting) _____ and _______. ◆ Receptor potential changes markedly with increases in low levels of stimulation ◆ Receptor potential increases only slightly with increases in high intensity stimulation ❖ Pacinian corpuscle Structural designs - pacinian corpuscle has a central nerve fiber extending through it’s core surrounded by multiple concentric layers Compression of the corpuscle causes mechanical deformation Ion channels open Sodium ions enter to interior of fiber (receptor potential) If threshold is reached, an action potential is elicited Initial amplitude of receptor potential increases rapidly With progressively stronger stimulus strength, amplitude is diminished but the frequency of repetitive action potentials increases Action potential is transmitted along the nerve fiber to the CNS This is how a receptor can be responsive to both weak and intense stimuli - “both light and deep pressure” ❖ Receptor adaptation Adaptation Initial receptor response: high Continued / frequent stimulation: diminished response Different types of receptors adapt at different rates Pacinian receptors are rapid adaptors (fraction of a second) Hair receptors adapt in 1 second Rapid adaptor receptors are better for sensing changes - “depolarize and repolarize” Aka rate receptors, movement receptors, phasic receptors Slow adaptor receptors Transmit impulses to the brain as long as stimulus is present Better for sensing constant conditions in the body ◆ Arterial baroreceptors ◆ Arterial chemoreceptors ◆ “Wouldn’t want a quick/sudden change in the bp, etc.” ❖ Nerve transmission - nerve fibers are categorized by function, size, myelination Nerve diameters: 0.5 micrometers - 20 micrometers Conduction velocity: 0.5 - 120 meters/second Two classification systems General classification (types A, B, C) A fibers → large/medium, myelinated, FAST B fibers → smaller, myelinated, preganglionic (ANS) C fibers → small, unmyelinated, SLOW Sensory nerve classification (group I - IV) Type I → large, myelinated, and FAST ◆ Fibers from muscle spindles, golgi tendon organs Type IV → small, unmyelinated, and SLOW ◆ Crude touch and pressure, tickle, aching pain, temperature ❖ *she said specifically to know this chart* ❖ Spatial and temporal summation: intensity Spatial summation - increasing signal strength is transmitted by using progressively greater numbers of fibers Example: painful stimulus across bigger area → more receptors are involved - bigger incisions hurt more Temporal summation - increasing signal strength is transmitted by increasing the frequency of nerve pulses in each fiber Same or nearby pre-synaptic neuron firing multiple times in close succession ❖ Neuronal pools - “think of overflow/overlap’ Groups of specially organized neurons that share common inputs, outputs, and functions CNS is composed of thousands → millions of neuronal pools Input fibers divide to create a stimulatory field If an input fiber excitatory impulse causes a neuron to fire, it is called suprathreshold If an input fiber excitatory impulse isn’t enough to reach threshold, it is called subthreshold (and those neurons are facilitated) Facilitated neurons can reach threshold if stimuli are received from another neuron The area of facilitated neurons is called the facilitated zone - aka subthreshold or subliminal zone If incoming fibers are inhibitory - they create an inhibitory zone ❖ Divergence - weak signals entering a neuronal pool excite greater numbers of nerve fibers leaving the pool Amplifying divergence: input signal spreads to an increasing number of neurons Divergence in multiple tracts: signal is transmitted in two directions ❖ Convergence - signals from multiple inputs excite a single neuron Convergence from a single source vs convergence from multiple sources Convergence allows summation of information so CNS can correlate, summate, and sort different types of information ❖ Reciprocal inhibition circuits Incoming signal causes output excitatory signal in one direction and an inhibitory signal going in another direction Characteristic for control of opposing muscle groups Prevent injury of weaker muscle - this is where she talked about glutes vs hamstrings One being contracted “automatically preventions contraction of the opposing muscle” ❖ Signal prolongation Afterdischarge: prolonged output discharge Can last milliseconds to minutes following the incoming signal Synaptic afterdischarge: a single input signal can cause a sustained output via a series of repetitive charges Reverberatory (oscillatory) circuit: feedback from the neuronal circuit feeds back to input the same circuit Varying degrees of complexity Some neuronal circuits continuously emit signals (continuous intrinsic neuronal discharge or reverberatory signals) ◆ Example: respiratory drive ❖ “Review questions of the first half of the content” - “examples of questions that will be on the exam” Large, myelinated, fast: A fibers → proprioception Small, unmyelinated, slow: C fibers → temperature, crude touch Specialized receptors: A beta fibers, 1a fibers ❖ Sensory pathways Most sensory input enters spinal cord through dorsal roots of spinal nerves Sensory information travels to brain via either: 1. Dorsal column (medial lemniscal system) aka DCML “Posterior column” “Enters at dorsal root, and crosses over in the lower level of the medulla” 2. Anterolateral system Anterior spinothalamic tract (crude touch) Lateral spinothalamic tract (pain, temp) “Enters at dorsal root, and crosses before ascending” ❖ DCML anatomy Sensory stimuli travels via type A-beta and C fibers (A-beta is DCML, not C) and enter spinal cord at the dorsal root ganglion The first-order neurons are those located in the dorsal root ganglia These are afferent → carry sensory information to the brain Nerve fibers divide in the spinal cord to medial and lateral branch Medial branch: enters through spinal root → dorsal column → brain Lateral branch: enters through dorsal horn → further divides until some enter dorsal column and travel to the brain, some terminated in spinal cord (reflexes), and some give rise to the spinocerebellar tracts Fibers then travel up fasciculus gracilis (below T6/Medial Branch) or fasciculus cuneatus (C2-T6/Lateral Branch)) These are second-order neurons (we don’t think this is right, second order start in medulla?) Fibers the decussate at the contralateral medial lemniscus (medulla) and ascend Terminate in the ventral posterior lateral nucleus of the thalamus - this is where the third order neurons are located She said specifically to know where 2nd and 3rd orders neurons are, and where they cross “1st order - dorsal root ganglia” “2nd order - gracillis or cuneatus, cross at medulla” “3rd order - thalamus” Key points Large, myelinated nerve fibers Rapid conduction velocity: 30-110 m/sec DCML carries localized touch, vibration, movement against the skin, joint sensation, proprioception, pressure Crosses over to opposite side at level of medulla Highly organized nerve fiber structure ❖ Somatosensory cortex Sensory signals terminated in the cerebral cortex Parietal lobe → reception / interpretation of somatosensory signals Occipital lobe → termination of visual signals Temporal lobe → termination of auditory signals Somatosensory area I Lies immediately behind central fissure in postcentral gyrus of the cerebral cortex Area I has the highest degree of localization, is much larger, and is most important Different parts of the body = different regions Size of region correlates with number of specialized receptors Each lateral cortex receives sensory information from the opposite side of the body Somatosensory area II Lies posterior to area I Function is not as well understood The homunculus Means “little human” Used to describe where 3rd order neurons go to transmit different anatomical impulses Used for lead placement by neurophysiologists using SSEP ❖ Proprioception - “position sense” There are two types of position sense: 1. Static position sense - conscious perception of the body in space 2. Kinesthesia (dynamic position sense) - rate of movement sense Receptors are located in joints (determine joint angulation), muscles (muscle spindles), and skin (tactile receptors) Neurons in the thalamus respond to the minimum and maximum joint rotation ❖ Anterolateral system Transmits sensory signals that do NOT require localization, discrimination Only transmission of pain, temperature, tickle, itch, and sexual sensations Conduction velocity is slower that in the DCML Spatial localization and intensity are poor Spinal cord anterolateral fibers originate in dorsal horn of laminae I, IV, V, VI Fibers cross immediately into the anterior commissure of spinal cord → anterior and lateral white columns → spinothalamic tracts → brain Spinothalamic tracts terminate in the brainstem and the thalamus Pain - reticular nuclei of the brainstem Pain - intralaminar nuclei of thalamus Tactile stimulation - ventrobasal complex of the thalamus Sensory stimuli travel from the periphery to the spinal cord before synapsing in the dorsal root ganglia The first order neurons are those located in the dorsal root ganglia These are afferents → sensory information to the brain Fibers synapse with second order neurons in the substantia gelatinosa Fibers deuces to the opposite side in the anterior white commissure, enter the anterolateral portion of the spinal cord, and ascend to the thalamus Enters the brainstem at the spinal lemniscus The third orders neuron cell body lies in the VPL (ventral posterolateral nucleus) of the thalamus ❖ Sensory pathways: review - “know the differences” DCML Consists of large, myelinated nerve fibers Rapid conduction velocity: 30-110 m/sec Carries signals to medulla via (mostly) the dorsal column Crosses over to opposite side at the level of the medulla Continues through brainstem to thalamus via the medial lemniscus Dorsal column carries localized touch, vibration, movement against the skin, joint sensation, pressure Highly organized nerve fiber structure Anterolateral Consists of smaller, myelinated or unmyelinated fibers Slower conduction velocity: 3-40 m/sec Signals enter the spinal cord from dorsal spinal nerve roots Synapse in the dorsal horns of the spinal grey matter Most cross to opposite side of the cord via anterior white commissure Ascend through anterior and lateral white columns of spinal cord Terminate at lower brainstem and thalamus Anterolateral system can transmit pain, warmth, cold, crude touch, tickle, itch, sexual sensations Much less organized nerve fiber structure ❖ Dermatomes Know the landmarks C4 - clavicle T10 - umbilicus T4 - nipples L4-5 - tibia T6 - xiphoid S2-5 - perineum ❖ Herpes Zoster (shingles) Caused by herpes virus - spread via airborne droplets or direct contact with actively viral shedding lesions Virus remains latent in trigeminal and dorsal (sensory) root ganglia, followed years later by reactivation to cause herpes zoster S/sx: pain and paresthesia localized to affected dermatome Thoracic or lumbar dermatome are most common If ophthalmic branch of trigeminal nerve is affected - it is considered a medical emergency as it is sight-threatening ❖ Peripheral nerve injuries Transection - partial or complete destruction of a nerve Compression - pressure on a nerve from bony prominence pressing against an internal or external surface Traction - stretching of a nerve against an immobile surface Injury mechanisms: ischemia, structural disruption, transection (cut) ❖ Pain Acute pain is protective Promotes withdrawal from painful stimuli Allows injury to heal Teaches the avoidance of painful stimuli Pain receptors are free nerves endings (“are everywhere”) that are located in skin and other tissues including: periosteum, arterial walls, joint surfaces, and tentorium in the cranial vault Respond to mechanical, thermal, or chemical stimuli Pain is classified into two types: fast pain and slow pain Dual pathways for pain transmission → fast-sharp pain pathway vs slow-chronic pain pathway Fast pain → fast/sharp pain pathway → neospinothalamic Transmitted by small type A-delta fibers Felt within 0.1 seconds Describes as sharp, pricking, acute, or electric pain Usually elicited by mechanical and thermal stimuli Slow pain → slow/chronic pain pathway → paleospinothalamic Transmitted primarily by type C fibers Felt after 1 second or more, then increases Described as slow burning, aching, throbbin, or chronic pain Usually associated with tissue destruction Can be elicited by mechanical, thermal, and chemical stimuli ❖ Pain receptors Nociceptors Sensory receptors that detect signals from damaged tissue or the threat of damage Pain receptors are free nerve endings Pain can be elicited by multiple types of stimuli (mechanical, chemical, thermal) Stimulated by bradykinin, serotonin, histamine, potassium ions, acids, acetylcholine, proteolytic enzymes Enhanced sensitivity by prostaglandins and substance P Average person receives pain at 45 degrees C (“aka the temp when tissues begin to be damaged”) Pain often correlates with rate at which damage to tissues is occurring - NOT with tissue damage that occurred Fast pain → mechanical and thermal stimuli Slow pain → mechanical, chemical, and thermal stimuli Pain receptors adapt very little (if at all) Excitation of pain fibers sometimes actually progressively increases (protective purpose) Hyperalgesia: unusually severe pain in situations where pain is normal, but pain is worse than it “should” be “If fibers/tissue is already damaged it can alter the perception/response to pain” ❖ Pain pathways: fast vs slow pain Pain fibers enter the spinal cord from the dorsal spinal roots The first-order neurons are those located in the dorsal root ganglia Within spinal cord, they take one of 2 pathways to the brain Neospinothalamic tract (fast-type pain) Pain fibers enter the spinal cord from the dorsal spinal roots The first-order neurons are those located in the dorsal root ganglia  Fast type A-delta fibers transmit mainly mechanical and acute thermal pain Glutamate is excitatory transmitter Fast-type pain can be localized better than slow-type pain ◆ Localization relies on sensory information from touch receptors Terminate mainly in lamina I (lamina marginalis) of dorsal horn where they excite second-order neurons of neospinothalamic tract Second-order neurons cross to opposite side of cord through the anterior commissure → anterolateral column → brain Paleospinothalamic tract (slow-chronic pain) Pain fibers enter the spinal cord from the dorsal spinal roots First-order neurons are those located in the dorsal root ganglia Transmits pain mainly via type C pain fibers plus some type A-delta fibers Peripheral fibers terminate in the spinal cord in lamina II and III (substantia gelatinosa) Most signals pass through 1 or more short fiber neuron before entering at lamina V Join fibers of the fast pain pathway Discuss at anterior commissure Follow anterolateral pathway to brain Most terminate in lower regions of the brain Pain is poorly localized type C pain fibers release both glutamate and substance P ❖ Pain sensations Referred pain: branches of visceral pain fibers synapse in spinal cord on the same second-order neurons that receive pain signals from the skin Visceral pain: pain from organs in abdomen and chest, highly localized types of damage to viscera seldom cause severe pain Diffuse visceral pain can be severe Nociception: processing of painful stimuli, involves four phases Transduction - converting painful stimulus into an electrical signal that is transmitted to the CNS Transmission - conduction of pain impulses along the a-delta and c fibers (primary-order neurons) → dorsal horn Perception - conscious awareness of pain, occurs primarily in the reticular and limbic systems and cerebral cortex Influenced by genetics, culture, sex roles, age, level of health, and past pain experiences Modulation - mechanisms that increase or decrease the transmission of pain signals (neurotransmitters, analgesic drugs, anesthesia, and nonpharmacologic interventions such as transcutaneous nerve stimulation, acupuncture, hypnosis, PT) ❖ Endorphins and enkephalins There are approximately 1-dozen naturally-occurring opiate like substances in the CNS Derived from pro-opiomelanocortin, proenkephalin, and prodynorphin Most important are beta-endorphin, met-enkephalin, leu-enkephalin, dynorphin Not completely understood Can activate analgesia and/or inactive pain pathways ❖ Special senses - vision, hearing, balance, gustation, smell Vision Eye anatomy Sclera - white of the eye, connective tissue; continuous with the dura mater around CN II Retina - cones/rods inner layer of the eye; macula is the reddish circle around the fovea Cornea - curved transparent outer layer Iris - colored muscular portion which elicits mydriasis and miosis Lens - behind the cornea; viscous gel; aqueous and vitreous humor Retina contains rods and cones - special photoreceptors that convert light energy into nerve impulses Rods mediate peripheral and dim light vision Cones are color and detail receptors Nerve impulses pass through the optic nerves (CN II) to the optic chiasm Fibers of the optic tracts terminate in the primary visual cortex in the occipital lobe of the brain Some fibers terminate in the hypothalamus and are involved in circadian regulation / sleep-wake cycle Glaucoma Eye is filled with vitreous humor and aqueous humor to give it shape, keep it from collapsing Aqueous humor: formed by ciliary body, flows through the pupil → anterior chamber of the eye → exits via the canal of schlemm  ◆ Maintains IOP (normal: 12-20 mmHg) ◆ Glaucoma, IOP can be as high as 60-70 mmHg Open angle glaucoma: most common, arises slowly and is non-painful, mismatch in AH production and drainage Closed angle glaucoma: can arise slowly or suddenly, “sudden variety” (10% of cases) is a medical emergency and the patient will lose their sight if it’s not surgically managed Retrobulbar block Retrobulbar block apnea syndrome - a complication of these blocks ◆ Injection of LA for a retrobulbar block that enters the optic nerve sheath can spread centrally and produce unconsciousness and apnea ◆ Treatment is supportive Intubation / ventilation Manage cardiac arrhythmia ◆ “Can cause hemorrhage” and “yes, CRNAs will do this” “Anesthesia and the eye” Intraocular pressure and anesthesia Increase IOP ◆ Succinylcholine (5-10 mmHg for 5-10 minutes) ◆ Ketamine? (“source varies”) ◆ Intubation - “SNS stimulation” Decrease IOP ◆ Inhalation anesthetics ◆ Propofol ◆ Opioids ◆ Benzodiazepines N2O should not be used in eye surgery especially if surgeon is placing a gas bubble Oculocardiac reflex - “five and dime” and Aschner reflex aka trigeminovagal reflex Traction on extraocular muscles, pressure on eyeball, and administration of a retrobulbar block - can all elicit a wide variety of cardiac dysrhythmias (bradycardia, ventricular ectopy, VF) Prevention and treatment strategies ◆ “Remove stimulus, deepen anesthetics, atropine/glycopyrrolate” “Common in pediatrics - strabismus repair” Visual evoked potentials (VEP) Performed by neurophysiologists during surgery with high potential for CN II damage Transsphenoidal hypophysectomy Craniotomy for disease near CN II Flashes of light are emitted, and electrodes placed over the occipital lobe, verify the integrity of the circuit VERY sensitive to anesthetic agents Anesthetic agents lower the amplitude and latency of the signal making it hard for the neurophysiologist to accurately assess integrity of the pathway Corneal abrasions Most common peri-op period ocular injury “One of my biggest pet peeves” - Dr. S ❖ Hearing and balance The ear is composed of external, middle, and inner structures External ear structures are the pinna, auditory canal, and tympanic membrane - only involved in hearing Middle ear is composed of the tympanic cavity, oval window, eustachian tube, and fluid - only involved in hearing Tympanic cavity contains three bones: malleus, incus, and stapes Inner ear is involved in hearing and equilibrium Includes the bony and membranous labyrinths that transmit sound waves Includes the semicircular canals and vestibule - help maintain balance Vestibular system: balance and spatial orientation, balance Small tract of neurons descend from the vestibular system to form the vestibulospinal tract The vestibulospinal tract again forms a DIRECT connection between position sense and efferent motor neurons (bypassing cognition) to keep the body in balance ❖ Gustation - “Some people are taste blind” ❖ Smell - “Least understood” “CN I” Lecture Two - Motor ❖ Sensory tracts Dorsal column medial lemniscus: “Larger, myelinated → faster” “Touch, vibration, joint sensation, pressure” Spinocerebellar tracts: “Proprioception” Spinothalamic tracts (anterolateral): “Technically 2 pathways” “Smaller, slower pain, temperature, crude touch, tickle, itch” ❖ Motor tracts Corticospinal tracts (pyramidal tracts) “Cortex → spine” Reticulospinal tract “Reticulo - means network” “Movement, posture, muscle control for walking, etc.” “Extrapyramidal - think dopamine” “Extrapyramidal symptoms → think of symptoms of psychiatric meds; also neuroleptic malignant syndrome is dopamine related (s/sx similar to MH) ❖ Motor efferents CNS order of motor control: The primary motor cortex (precentral gyrus of the frontal lobe) determines the goal of movement and its consequences “Cortex involvement is needed for dancing aka complicated/coordinated movement” Basal ganglia provides the boost that turns intention into an actual movement - excitatory and inhibitory function (gateway) “Parkinson’s → slow to get up, the intention is there but the transmission of the intention is the issue” Cerebellum determines the correct sequence of commands that will allow the goal to be achieved ❖ Intro: motor system Motor transmission is via a 2-neuron pathway Motor responses begin in the spinal cord (simple reflexes), brain stem (more complicated responses) and cerebrum (most complicated muscle skills) Upper motor neurons: transmit information from the brain → brainstem or spinal cord Neurotransmitter: glutamate Lower motor neurons: transmit information from the spinal cord → muscles and glands Neurotransmitter: acetylcholine Motor pathways are efferent (carrying impulses away from the CNS) ❖ Interneurons Present in all areas of cord gray matter (dorsal horns, anterior horns, areas between them) Small and highly excitable Can fire as rapidly as 1500x/second 30x more interneurons than anterior motor neurons Corticospinal tract consists primarily of interneurons ❖ Anterior motor neurons Innervate skeletal muscle Located in each segment of the anterior horns of the gray matter Largest (50-100% larger than most other neurons) Give rise to nerve fibers that exit spinal cord via anterior roots and directly innervate skeletal muscles Two types: Alpha motor neurons - innervate large skeletal muscles Gamma motor neurons - innervate intrafusal fibers of the muscle spindle “Even when you’re sitting still your muscles have tone” ❖ Motor pathways Transmit information from the brain to: Voluntary (skeletal) muscles Smooth muscles Cardiac muscles Some glands Motor pathways are efferent (carrying impulses away from the CNS) Motor responses begin in the spinal cord (simple reflexes), brain stem (more complicated responses), and cerebrum (most complicated muscle skills) “Involuntary (due to constant tone) - heart rate, breathing, gag reflex, swallowing, contraction of muscle in response to stretch” “Humans have over 500 skeletal muscles - we need them all to be coordinated, can get out of whack due to many things” ❖ Motor functions Cerebellum - determines the correct sequence of commands that will allow the goal to be achieved Primary motor cortex - determines the goal of movement and its consequences Basal ganglia - provides the “boost” that turns intention into actual movement - excitatory or inhibitory (gateway) Corticospinal tract - voluntary muscles of the trunk and extremities Cranial nerves - supply voluntary muscles of head and neck ❖ Cerebral motor cortex Located anterior to the central cortical sulcus → “most complicated motor movements” Cerebral motor cortex occupies the posterior one-third of the frontal lobe Motor cortex consists of 3 areas: Primary motor cortex - muscles of hands, speech “Usually contraction of muscles” “more than half” “usually control a whole movement (arm extension and coordinating the multiple muscles it takes to do so) rather than just one muscle” Premotor area - patterns of movement, mirrored tasks “Mirroring someone is a different area than just doing it on your own” Supplementary motor - cortex bilateral movements “Think climbing, you are coordinating both sides” ❖ Specialized motor areas Broca’s area: motor speech area; has to do with word formation “Muscles of lips, tongue, and throat to formulate speech” “Know what they want to say, but can’t get it out - may get words out but not full sentences” Voluntary eye movement field: controls voluntary eye movement including blinking “Protective; automatically blink if something comes near the face” Head rotation area: stimulation in this area directs the head toward objects “If something flies past face you automatically follow it” Area for hand skills: damage to this area causes motor ataxia (difficulty with skilled movement) “A much bigger area of the brain than head rotation, eye movements, etc.” ❖ Transmission of signals from the motor cortex → muscles Corticospinal tract (aka pyramidal tract) Most important output pathway! Originates from: Primary motor cortex (30%) Premotor and supplementary motor cortex (30%) Somatosensory area (40%) Indirect / alternative pathways: accessory pathways - “mesencephalon, corticospinal tract” Cranial nerves: supply voluntary muscles of head and neck “All parts if the body except for the face” “Brain → medulla → decussate → pyramids of medulla ❖ Corticobulbar tracts: CN - III, IV, V, VI, IX, X, XI, and XII Movements of eyes, tongue, chewing, expressions, and speech ❖ Motor pathways: lateral corticospinal tract (pyramidal)* Originates in precentral gyrus of the frontal lobe Highly organized (neurons supplying specific areas of the body are grouped together) Motor fibers for all parts of the body except the face Axon travel from cortex → through the internal capsule → midbrain (basis pedunculi) → medulla → lateral corticospinal tract (aka pyramidal tract) → spinal cord Most fibers decussate in lower medulla Those that do not cross at medulla travel via ventral corticospinal tracts and cross in neck/thorax Motor nerves exit the spinal cord via the anterior horn ❖ Intrinsic muscle control Muscle spindles - “balance, prevent excessive stretch - if running and you overstretch a muscle you’ll get a pain signal” Found in belly of skeletal muscles Send sensory info to the brain about muscle length or rate of change of length 2 sensory fibers to differentiate between slow and fast stretch “Static → slow increase in length/tension” “Dynamic → fast increase in length/tension” Excited by small gamma motor nerve fibers - originate from type A-gamma motor neurons in anterior horn the spinal cord “Underlying constant muscle tone → due to spindles” Golgi tendon organs Located in the muscle tendons Transmit information about tendon torsion or rate of change of tension Consist of an encapsulated sensory receptor through which muscle fibers must pass Organ is stimulated when the bundle of fibers is tensed ❖ Reflex responses Flexor reflex: Stimulation of pain endings (nociceptive reflexes, pain reflex) causes that part of the body to be withdrawn from stimulus Flexor reflex pathways pass directly from neuronal pool in spinal cord to motor fibers → “don’t have to go all the way to brain for motor response” Activates diverging circuits to spread impulse to: Necessary muscles for withdrawal → “coordination of all muscles needed for reflex/response” Circuits to inhibit opposing muscles (reciprocal inhibition circuits) Circuits to cause after-discharge (lasts a few seconds after stimulus is over) ◆ After-discharge duration depends on intensity of initial stimulus ◆ This after-discharge holds the irritated part away from the stimulus for 0.1-3 seconds after irritation is over- “don’t do anything for a millisecond after, delay until message gets to the brain → protective” Crossed extensor reflex: Extension of the opposite limb to “push away” the entire body from the spinal stimulus Video on this ❖ Clinical relevance: disorders of the motor system Upper motor neuron disease: Increased DTRs Increased muscle tone Positive Babinski sign Spastic paralysis Lower motor neuron disease: Decreased DTRs Decreased muscle tone Negative Babinski sign Flaccid paralysis / muscle atrophy Where is injury in relation to decussation? Above decussation, paralysis on opposite side of body Below decussation, paralysis is on the same side of the body “Pt with strokes → injury above the level → contralateral symptoms”  “Disorders are classified on if upper, lower, or both and the level of the injury” “Most cross at the medulla → not all” “Upper motor neuron - brain → spinal cord” “Reflexes intact” “Brain, cortex” “Injury: thrombosis; aneurysm; brainstem (demyelination (MS), trauma, degenerative disease (parkinsons), ALS, cancers/neoplasms; spinal cord (neoplasms, demyelination, ALS) “Lower motor neuron - spinal cord → effector” “No reflexes, no constant tonicity, flaccid paralysis” “Dr. S’s husband → occlusion myositis → hands are atrophied, disrupted impulse between brain and hands” ❖ Clinical relevance: movement disorder terminology Ataxia - inability to coordinate muscle activity Athetosis - involuntary mvmts of flexion/extension, pronation/supination of hands, toes, and feet; slow; writhing-type mvmts Ballismus - jerking, swinging, sweeping motions of the proximal limbs Bradykinesia / hypokinesia - decrease in spontaneity and movement Chorea - irregular, spasmodic, involuntary movements of limbs or facial muscles, often with hypotonia Cogwheel rigidity - resistance to movement; rigidity decreasing to stiffness after movement begins Dystonia - abnormal tonicity; difficulty maintaining posture Hyperkinesia - excessive motor activity Tic - repeated, habitual muscle contractions; movements that can be voluntarily suppressed for short periods Tremor - oscillating, repetitive movements of whole muscles; irregular, involuntary contractions of opposing muscles ❖ Clinical relevance: cerebral palsy Caused by damage to upper motor neurons from an event that occurs prenatal, perinatal or postnatal (cerebral anoxia, hemorrhage, and other neurologic insult) Classified by the type of motor dysfunction: Spastic - inability of muscles to relax Hemiplegia - involving one arm and one leg on the same side of the body Diplegia - involving both legs Quadriplegia - involving all four extremities, the trunk, and neck muscles Athetoid or dyskinetic - inability to control muscle movement Ataxic - inability to control balance and coordination Clinical manifestations: Altered body movements and muscle coordination Developmental delays Not a progressive disease ❖ Clinical relevance: ALS (amyotrophic lateral sclerosis) Degenerative disease of motor neurons Exact cause unknown (glutamate excitotoxicity and/or oxidative stress?) No known cure Affects both upper and lower motor neurons Leads to the destruction of NMJ Rapid progression, fatal disease Symptoms appear first in arms, hands, legs, and swallowing muscles → muscles gradually weaken, waste away, and twitch ❖ Clinical relevance: spinal cord injury SCI impairs the transduction of afferent and/or efferent neural impulses Damage to the gray matter of the central cord may result in loss of motor neurons and interneurons In complete injury, sensation and motor function below the level of injury are lost Categorization of PARTIAL cord transections Central cord syndrome Anterior cord syndrome Brown-Sequard syndrome - “test on the exam” “Partial transection - loss of motor/proprioception on one side and pain/temp on the other”  Lecture Two - Autonomic Nervous System ❖ Sympathetic nerve distribution (thoracolumbar) “How close are sympathetic nerves to → effector” “Close proximity” “A ton of nerves coming off one pre-ganglionic” “Diffuse and generalized” ❖ Parasympathetic nerve distribution (craniosacral outflow) “Some synapse early, some go all the way to organ/effector” “Postganglionic in or near effector organ” “More focused - less nerves off of preganglionic nerve” “Discrete and limited” CN: III, VII, IX, X and S2-4 ❖ Cervical ganglia - provide sympathetic innervation to head, neck, arms, and upper chest Cervical ganglia are divided into superior, medial, inferior cervical ganglia Inferior cervical ganglion fuses with 1st thoracic ganglion in 80% of individuals to form the stellate ganglion (aka cervicothoracic ganglion) - “loss of smell in covid; blocks here would ‘reset’ stellate ganglion to recover sense of smell” Stellate ganglion blocks are used to treat: chronic regional pain syndromes, craniofacial hyperhidrosis, refractory angina, postherpetic neuralgia, PTSD, PVD, and long-covid Horner’s syndrome: ptosis, miosis, and anhidrosis “If doing a higher block/upper extremity → look for this” “Also look for it if you’re trying to block stellate ganglion specifically” ❖ SNS and PSNS Nerve Fibers Preganglionic nerve fibers: Myelinated Diameter: < 3mm Conduction velocity: 3-15 m/sec Acetylcholine Postganglionic nerve fibers: Unmyelinated Conduction velocity: 2 m/sec (SLOW!) Parasympathetic: acetylcholine Sympathetic: norepinephrine ❖ Physiologic anatomy of ANS SNS and PSNS are the efferent (motor) component of the ANS Most organs receive fibers from both divisions → “balance between the two that ultimately decides what happens” Exceptions: sweat glands - innervated by only SNS fibers 2 neuron system Two neuron (bipolar) chain from the CNS to the effector organ Preganglionic - “originates in CNS → transmits to preganglionic → connects with → postganglionic” Postganglionic - “transmits to effector organ” ❖ Receptors on effector organs Acetylcholine, norepinephrine, epinephrine are secreted from autonomic nerve endings Requires binding with specific receptors on effector cells Binding causes a conformational change → excitation or inhibition Opens or closes an ion channel → alters permeability of cell membrane to various ions Second messenger enzymes → activation or inactivation of enzyme on interior of cell ❖ SNS and PSNS neurotransmitters CHOLINERGIC = ACETYLCHOLINE ADRENERGIC = NOREPINEPHRINE All preganglionic nerve fibers in both are cholinergic (acetylcholine) Almost all parasympathetic postganglionic nerve fibers are cholinergic (acetylcholine) Most sympathetic postganglionic nerve fibers are adrenergic (norepinephrine) ❖ Acetylcholine synthesis - “must know” “Terminal endings of cholinergic fibers → synthesis of choline + acetyl-Coa (with enzyme choline transferase) = ACh “Broken down by: acetylcholinesterase” ❖ Norepinephrine synthesis “Terminal nerve endings of adrenergic fibers” “80% of norepinephrine in medulla gets made into epinephrine with enzyme phenylethanolamine” ❖ Norepinephrine and epinephrine metabolism “MAO - neuronal endings” “COMT - tissues, glial cells, organs, muscles, etc.” “Suspected pheochromocytoma → can’t draw blood levels, do a urine test for VMA” ❖ Cholinergic receptors Acetylcholine activates both muscarinic and nicotinic receptors → “reversal of NMBs - we want some effects from reversals, not others (why we give glycopyrrolate)” Muscarinic are found on all effector cells that are stimulated by postganglionic cholinergic neurons of either PSNS or SNS Nicotinic are found in the autonomic ganglia at the synapses between the preganglionic and postganglionic neurons of both SNS and PSNS - also found outside the ANS (NMJ) ❖ Adrenergic receptors Alpha receptor activation: can cause excitation or inhibition Vasoconstriction, iris dilation, intestinal relaxation, intestinal sphincter contraction, pilomotor contraction, bladder sphincter contraction, inhibits neurotransmitter release Beta receptor activation: can cause excitation or inhibition Vasodilation, cardioacceleration, increased contractility, intestinal relaxation, uterus relaxation, bronchodilation, calorigenesis, lipolysis, bladder wall relaxation, thermogenesis “Beta 1 - heart and Beta 2 - lungs”  Norepinephrine and epinephrine activate both alpha and beta receptors Norepinephrine: primarily on alpha receptors Epinephrine: works equally on both alpha and beta receptors “May be dose dependent → think how we have different dose ranges for different outcomes with dopamine” ❖ Table from Baby Miller “Sympathetic is not all excitatory and parasympathetic is not all inhibitory” - she said this like 3x in a row A1 - vasoconstriction A2 - digestion, inhibition of NT release (think precedex) B1 - cardiac B2 - lungs B3 - thermogenesis/metabolism ❖ Postganglionic breakdown of ACh and norepi ACh Broken down into acetate and choline by the enzyme acetylcholinesterase Same as mechanism at NMJ Choline is ‘recycled’ to make more ACh Norepinephrine Three mechanisms terminate activity of norepinephrine in seconds: 1. Active reuptake (50-80% of norepi) 2. Diffusion away from nerve endings → body fluids and blood 3. Destruction by tissue enzymes (MAO, COMT) ❖ Anesthesia goal for managing the ANS - “modulate ANS; control outcomes; balance and maintain perfusion” Goal: railroad tracks How: “perfectly anticipate and appropriately manage the different stages of care - laryngoscopy increase HR and BP; wait post intubation for surgery start - dip in BP and HR; appropriate pain management and appropriate reversal doses” ❖ ANS: controls BP, GI motility/section, bladder emptying, sweating temperature Activated by centers in spinal cord, brainstem, and hypothalamus Influenced by limbic system (memory/emotion/fear) ANS can respond rapidly Can increase HR to 2x normal within 3-5 seconds Can increase BP to 2x normal in 10-15 seconds ❖ Parasympathetic - rest and digest or feed and breed ❖ Sympathetic - fight or flight ❖ Homeostasis between PSNS and SNS ❖ Higher level organization of SNS Hypothalamus - “integration of PSNS and SNS - example: passing out at sight of blood - vagal & limbic” Long-term BP control Reactions to physical and emotional stress Sleep Sexual reflexes  Medulla oblongata and pons “Momentary” hemodynamic adjustments Sequence and automaticity of ventilation Maintaining constant “tonicity” Nucleus tractus solitarius relays afferent chemoreceptor and baroreceptor for SNS response “Purpose of decreases BP and HR in trauma: less blood loss ❖ SNS - thoracolumbar system Originates: T1-L2 Preganglionic neuron lies in intermediolateral horn of spinal cord Passes through ventral root (“know that”) → white ramus → sympathetic chain ganglia Synapse with postganglionic neuron Postganglionic neuron originates in either sympathetic chain ganglia or peripheral sympathetic ganglia and transmits impulse to the effector organ Exception: adrenal medulla has only preganglionic fibers (ACh) ❖ PSNS - craniosacral system Has preganglionic and postganglionic neurons Originate in brainstem and sacrum Also found in CN III (oculomotor), VII (facial), IX (glossopharyngeal), and X (vagus) Sacral outflow originates in intermediolateral gray horns of sacral nerves Vagus nerve accounts for 75% of PSNS activity ❖ Parasympathetic and sympathetic tone Constant activity of SNS and PSNS maintain basal rate of activity Allows a single nervous system to both increase and decrease activity of a stimulated organ Sympathetic tone causes baseline blood vessel constriction Parasympathetic tone maintains baseline GI motility Adrenal medulla maintains basal secretion Epinephrine 0.2 mcg/kg/min Norepinephrine 0.05 mcg/kg/min Enough to maintain normal BP even if all direct innervation was removed → “back-up for survival” ❖ Adrenal medulla Preganglionic sympathetic nerve fibers pass W/O SYNAPSING from spinal cord → sympathetic chain → adrenal medulla Innervated by preganglionic fibers that secrete epinephrine and norepinephrine (not ACh) ^^^Preganglionic secretes ACh which stimulates the medulla to secrete epi and norepi - confirmed by Schless Effects: same as sympathetic stimulation Prolonged DOA (5-10x) because they are removed slowly from the blood Organs are stimulated in two ways (SNS and adrenal medulla) Dual mechanism of sympathetic stimulation = safety Adrenal medulla also can stimulate structures that NOT innervated by direct sympathetic fibers “Adrenal medulla → 80% norepi gets turned into epi” “Adrenal cortex - 3 zones: GFR” “Glomerulosa: salt (mineralocorticoids), fasciculata: sugar (glucocorticoids), reticularis: sex hormones” ❖ Sweat glands SNS stimulation increases sweat production of sweat glands Sympathetic fibers to most sweat glands are cholinergic (ACh) - “stress related, it’s stressful running from a bear - its norepi” Exception: adrenergic fibers to palms and soles (“palmar hyperhidrosis”) ❖ Autonomic reflexes Baroreceptor reflex: Stretch receptors in walls of major arteries (carotid artery, aortic arch) detect stretch “High pressure” impulses are sent to the brain stem Sympathetic impulses inhibited / parasympathetic impulses increase BP returns to normal Gastrointestinal reflexes: Small of food increases salivation and GI secretion of digestive juices Rectal emptying reflex / defecation  Sexual reflexes Other reflexes Pancreatic secretion, gallbladder contraction, kidney excretion of urine, blood sugar concentration “Phenyl → increase bp via venous and arterial vasoconstriction → increases preload → baroreceptors feel stretch → decrease in HR → CO stays the same / doesn’t increase” “Ephedrine stimulates the release of endogenous catecholamines → increase HR/BP → will eventually run out of them / deplete them” “Trauma patients - no ephedrine due to decreased catecholamine stores” “Spinal sympathetic block → if high enough spinal the HR will decrease → if HR is low enough and block is high enough don’t use phenyl” ❖ Denervation injury - “intrinsic tone is lost” Intrinsic compensation for denervation injury Intrinsic tone in smooth muscle of vessels increases following injury Chemical adaptations - “adaptations can take months” Increased sensitivity to circulating catecholamines - “upregulation → exaggerated response to injected catecholamines” Eventually restores almost normal vasoconstriction Parasympathetic compensation may require many months Denervation supersensitivity (upregulation) Can see enhanced effect of administered catecholamines ❖ Autonomic dysreflexia Condition that emerges after a SCI Usually above T6 (injury) Dysregulation of ANS leads to an uncoordinated sympathetic response that may result in a potentially life-threatening hypertensive episode when there is a noxious stimulus below the level of the SCI Noxious stimuli consist usually of bladder or bowel distention - “catheterization, full bladder” The higher the injury, the greater the severity of CV dysfunction Significantly increased risk of stroke by 300-400% “Neurologic procedures → general anesthesia could help block all of it” “Severe htn, bradycardia, less sweating, facial flushing, severe HA, nasal stuffiness” ❖ Autonomic pharmacology Drugs may be used to either mimic or block the action(s) of the autonomic nervous system Sympathomimetics (adrenergic agonists): mimic the action of catecholamines; increase SNS activity Cholinomimetics: mimic the effect of acetylcholine; increase PSNS activity Adrenergic antagonists (adrenergic blockers): block the action of catecholamines; decreases SNS activity Anticholinergics: block the effect of acetylcholine, decrease PSNS activity “Just because it mimics, doesn’t mean that it stimulates the sub receptors equally” Note: drug effects depend on specific receptors affected! Note: need to know / understand how the medication works (ie: does it activate the receptor directly? Increase release of naturally occurring neurotransmitters from storage vesicles? After the breakdown of neurotransmitters?) ❖ Sympathomimetics “Know where, receptors, agonists/antagonists” “Will not ask meds and receptors, will ask type and effects” ❖ Adrenergic antagonists Adrenergic antagonists prevent activation of adrenergic receptors Used to treat htn, angina, BPH, migraine headaches Effect depends on adrenergic receptor type(s) Alpha-adrenergic blocking agents: Beta-adrenergic blocking agents: Examples - Selective Beta-1: atenolol, metoprolol, esmolol Nonselective: Beta-1 and Beta-2: propranolol Beta-1, Beta-2, and Alpha-1: labetalol, carvedilol All adrenergic antagonists produce reversible (competitive) blockade EXCEPT: Phenoxybenzamine - not reversible ❖ Cholinergics (cholinomimetics) Cholinergic medications stimulate the PSNS Directly activate cholinergic receptors (acts like ACh) Indirectly by preventing the breakdown of acetylcholine Two types of cholinergic receptors: muscarinic and nicotinic Muscarinic: brain, glands (salivary), smooth muscle (GI tract, GU) Nicotinic: autonomic ganglia, NMJ, adrenal medulla Remember: Anticholinergics: block the action of acetylcholine (decreases PSNS activity) Anticholinesterases: block the action of acetylcholinesterase (increases PSNS) ❖ Cholinergic crisis: Excessive muscarinic stimulation and depolarizing neuromuscular blockade Sludge and the Killer B’s S - salivation L - lacrimation U - urination D - diaphoresis / diarrhea G - gastrointestinal cramping E - emesis B - bradycardia B - bronchospasm B - bronchorrhea “Treat with: atropine, anticholinergics; typically need to be vented until it’s worked through” ❖ End comments:“Stay out of the weeds” Sensory vs Motor Afferent vs Efferent Tracts and where they cross Parasympathetic vs sympathetic effects and NTs Know how types of meds work - don’t memorize all meds