ANS Study Guide PDF

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)...

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