Neurophysiology 751 Canvas.pptx

751 Neurophysiology Terry Wicks, DNP, CRNA Neurons  Cell body  Axon  Terminates near another cell body  Dendrite  Presynaptic terminal  Synaptic cleft  Receptor Classificati on of Nerve Fibers Defining...

751 Neurophysiology Terry Wicks, DNP, CRNA Neurons  Cell body  Axon  Terminates near another cell body  Dendrite  Presynaptic terminal  Synaptic cleft  Receptor Classificati on of Nerve Fibers Defining  Afferent fibers transmit information to the Characterist CNS from the periphery ics  Efferent fiber transmit information to the periphery from the CNS  Conduction speed increases with fiber diameter  Nodes of Ranvier:  Interruptions in the myelin sheath (q 1-2 mm)  Saltatory conduction  Dramatically reduces energy required for repolarization   Electrical potential exist across nearly all cell The Action membranes Potential  Due differential distribution of N+ and K+ ions (3:2)  Maintained by sodium-potassium ATPase  Resting membrane potential is typically (-60 to -90 mV)  Open channels allow ions to flow in the direction of their concentration gradient.  Depolarization: Open sodium channels  Repolarization: Closure of sodium channels and opening of potassium channels   Action potentials are Action conducted by depolarization along the entire length of Potential the muscle or nerve cell Propagatio  Occurs in less than 1 millisecond n  Absolute refractory period: due to preponderance of inactivated sodium channels  Relative refractory period: an action potential can occur if a critical number of sodium channels can be activated. Implication s of  Hypocalcemia leads to inability to sodium channels to close (tetany) Abnormal  Hypercalcemia decreases cell permeability Ion to sodium ions (decreased excitability)  Hypokalemia results in membrane Distributio hyperpolarization and decreased excitability n (skeletal muscle weakness)  Local anesthetics block sodium channels and decrease myocardial contractility.   Neurotransmitters (chemical mediators) are Neurotransmitt stored in presynaptic vesicles ers & Receptors  Released in responses to the arrival of an action potential  May be inhibitory or excitatory  Depending on ion selectivity  Site or location of the receptor  May modulate the sensitivity of receptors to other neurotransmitters (glycine and NMDA receptor)  Volatile agents will generally inhibit excitatory receptors and potentiate inhibitory neurotransmitter. Receptors: By Location  Surface receptors:  Ligand gated ion channel receptors  Enzyme linked transmembrane receptors  Guanine nucleotide binding protein (G protein receptors)  Intracellular receptors: steroid and hormone receptors.   Components: G Protein-  Receptor protein  3 G-proteins (α,β, and γ) Coupled  Effector mechanism Receptors  Ligand binding to the surface protein stimulates a conformational change which activates a Gα coupled protein in the interior of the cell  May be stimulatory or inhibitory  Many hormones and drugs act through G protein-coupled receptors:  Catecholamines  Opioids  Anticholinergics  Antihistamines G Protein-  Dopamine: Inhibitory or excitatory depending on the receptor-50% of CNS catecholamines Coupled  Norepinephrine: Prominent in the RAS & Transmitte hypothalamus- important in pain modulation  α 1 excitatory rs  α 2 inhibitory  Substance P: excitatory for pain  Endorphins: endogenous opioids  Serotonin: CTZ in the CNS, common in the gut  Histamine: Prominent in the RAS and hypothalamus Ion Channels 1. Channel domains 2. Outer vestibule 3. Selectivity filter 4. Diameter of the selectivity filter 5. Phosphorylation site 6. Cell membrane   Ions flow through open channels according to Ion their concentration gradient.  Extracellular concentrations are high for: Channels  Sodium  Calcium  Chloride  Intracellular concentrations are high for:  Potassium  Inward rectifying channels allow potassium to flow into a cell according to an electrical gradient  Variations of concentrations and currents will depolarize or hyperpolarize the cell membrane.  Ion channels open when the cell membrane depolarizes Excitatory  Facilitate the influx of ions into the cell leading Ligand to depolarization Gated Ion  Acetylcholine Channels:  Muscarinic receptors: Inhibitory in the PNS through G protein coupled receptors Acetylcholi  Non-specific nicotinic receptors: mediate arousal, are inhibited by volatile inhalation agents. Allow ne passage of sodium, calcium and potassium ions.  Enhance the release of other neurotransmitters  The neurotransmitter at the NMJ   Glutamate is the major excitatory amino acid Excitatory neurotransmitter in the CNS Ligand  Non-selective channels: Gated Ion  Sodium-inward  Calcium-inward Channels:  Potassium-outward Glutamate  Depolarizing and excitatory  Inotropic receptors for NMDA, AMPA, and kainite. NMDA receptors are associated with neuropathic pain and opioid tolerance  Metabotropic receptors are linked to G proteins modulating intracellular second messengers   GABA is the major inhibitory Inhibitory neurotransmitter in the brain. Ligand  The GABA receptor binds two molecules of Gated Ion GABA  The channel opens allowing chloride ions to Channels: enter the cell leading to hyperpolarization GABA  Target for:  Propofol  Etomidate  Thiopental  Benzodiazepines allosterically increase the sensitivity of the receptor to GABA Inhibitory Ligand Gated Ion  The principle inhibitory neurotransmitter in the spinal cord. Channels:  Increases chloride conductance Glycine  Glycine receptors are present in the brain  More later… Voltage  Channels which open and Gated Ion close in response to Channels changes in voltage across cell membranes  Present in:  Neurons  Skeletal muscle  Endocrine cells  The site of local anesthetic action Receptor Concentrati  Receptor populations are not static… on  Increased circulating concentrations of ligands often leads to a decrease in receptor density (down regulation).  Drug-induced antagonism of receptors often results in an increase in receptor density (up regulation)  Site of transmission of an action potential The from the presynaptic membrane to the postsynaptic membrane. Synapse   Presynaptic membrane contains vesicles of The neurotransmitter and a reuptake pump  Synaptic transmission begins with the arrival of Synapse an afferent action potential at the voltage gated calcium channel  Influx of calcium occurs, binding to the release apparatus on axonal and vesicular membranes and triggers fusion of the vesicle to the cell membrane and exocytosis.  Neurotransmitter is released into the synaptic cleft and binds to the postsynaptic membrane, stimulating an action potential in the dendrite of the efferent nerve.  Magnesium antagonizes the effects of calcium.   Defined as conscious memory of events during anesthesia Awareness  Administration of neuromuscular blocking drugs increases & Recall the risk of unintended awareness under general anesthesia  Memories can be:  Explicit (conscious) spontaneous recall recognition memory  Implicit (unconscious) altered behavior or performance due to experiences that are not consciously recalled.  Depending on risk stratification, occurs as often as 1- 5/1000 cases.  Often attributed to intentional or unintentional administration of low concentrations of administered anesthetic  Volatile inhalation agents suppress memory in a dose dependent fashion.   Indicators of awareness are Recognitio masked by anesthesia drugs-opioids, beta blockers, n of neuromuscular blocking Awareness drugs  Heart rate  Blood pressure  Skeletal muscle movement  EEG interpretation and assessment of somatosensory evoked potential patters may increase the ability to detect inadequate anesthesia   Processed EEG combining the Bispectral characteristics of various EEG waveforms to produce a Index dimensionless number between 1- 100.  Values correlate with depth of anesthesia  0: isoelectric EEG  < 60 low probability of recall  100 wide awake  May allow for reduced drug use and more rapid return of consciousness  An alternative is to maintain end tidal concentrations of inhalation agents at 0.7-1.3 MAC   Somatosensory EP: stimulation of a peripheral Evoked nerve (wrist or ankle) with a low-voltage current. Monitoring transmission to the Potentials somatosensory cortex. Volatile inhalation block the response in a dose dependent manner.  Motor EP: requires direct (epidural) or indirect (trans-osseous) stimulation of the brain or spinal cord. Assesses motor pathways. Use during spinal surgery may eliminate the necessity of an intraoperative wake up.  Auditory EP: Arise from brainstem auditory pathways.  Visual EP: Generated by light emitting diodes placed over the patient’s closed eyes   Nausea: conscious Nausea & recognition of excitation in the vomiting center of the Vomiting medulla  Afferent inputs are SNS, and PNS  Motor pathways through CN V, VII, IX, X, and XII are responsible for diaphragmatic and abdominal muscles used for vomiting  Medullary vomiting center is located near the 4th ventricle Nausea & Vomiting  Vomiting center afferents:  Chemoreceptor trigger zone (CTZ)  Cerebral cortex  Labyrinthovestibular center  Neurovegetative system  The CTZ is not protected by the BBB and is sensitive to systemic circulatory stimuli as well as from CSF   Peripheral nerves extend from the dendrite to the DRG (cell body) and to the spinal cord via the dorsal root. Sensory  Dendrites conduct impulses towards the cell Pathways body  Axons conduct impulses away from the cell body  Sensory nerves synapse in the dorsal horn  Ascending fibers transmit sensory information to the brain  Dorsal columns: cross before ascending  Spinocervical tracts: ascend through ipsilateral tracts  Anterolateral spinothalamic tracts: cross in the anterior commissure  All sensory pathways to the cortex traverse the thalamus Schematic Diagram Peripheral  Aα fibers leave the spinal cord via the anterior Motor roots, innervating skeletal muscle Responses  Upper motor neurons originate in the cerebral cortex or brainstem, crossing in the medulla prior to traveling down the anterior or lateral corticospinal tracts.  Upper and lower motor neurons synapse in the ventral horn of the spinal cord.  Lower motor neurons originate in the spinal cord, traveling directly to muscle Autonomic  Autonomic nervous system controls the visceral functions of the body Nervous  Activation centers reside in: System  Hypothalamus  Brainstem (ANS)  Spinal cord  Components:  Sympathetic nervous system (SNS)  Parasympathetic (PNS)  Enteric (ENS)  Most autonomic systems are in balance between SNS and PNS influence Autonomic Nervous System   Nerves originate at spinal cord Sympathet segments T1-L2 ic Nervous  Cell bodies of preganglionic neurons are located in the System intermediolateral horn of the spinal cord  Axons are myelinated β fibers  Fibers travel through the paravertebral sympathetic chain and synapse with cell bodies of post ganglionic neurons.  Post-ganglionic sympathetic fibers then travel to the various peripheral organs. Parasympath etic Nervous  Nerves leave the CNS System through CN III, V, IX, X  Vagus n. is the largest of the four  Sacral components include S2-3, occasionally S1 & S4  Preganglionic fibers travel to, or near, the innervated organ Physiology of the ANS  All autonomic preganglionic fibers release Ach as the neurotransmitter  Sympathetic postganglionic fibers release norepinephrine (adrenergic)  Parasympathetic postganglionic fibers release Ach (cholinergic) Norepinephri ne  Synthesized in the cytoplasm of the postganglionic sympathetic nerves and stored in synaptic vesicles.  After release norepinephrine is recycled or metabolized  Reuptake (80%)  Metabolism in the cytoplasm (MAO) or liver (COMT)  The primary metabolites are excreted in the urine as vanillylmandelic acid (VMA) Acetylcholi  Choline and acetyl coenzyme A are ne combined in the presence of acetyltransferase to form acetylcholine  Ach is stored in synaptic vesicles  After release Ach is rapid metabolized by acetylcholinesterase to choline and acetate.  Choline is taken up and recycled  Plasma cholinesterase metabolizes small amounts of Ach  Adrenergic Cholinergic Receptor Receptors Receptors Variations  Nicotinic  Alpha1  Muscle  Brain: control the  Alpha2 release of other  Beta1 (cardiac) neurotransmitters  Beta2 (non-cardiac)  Muscarinic  M1  Dopamine1  M2  Dopamine2  M3  M4  M5 Aging &  Clinical manifestations include:  Orthostatic hypotension ANS  Postprandial hypotension Hyp0thermia Dysfunctio   Heat stroke n  Due to decreased ability to adapt to stress and reduced number of adrenergic prejunctional terminals.  Plasma epinephrine and β adrenergic receptor concentrations are unchanged.  Response to β adrenergic stimulation is blunted in the elderly