MPAS; PAEP7002 Autonomic Nervous System PDF

MPAS; PAEP7002 Autonomic Nervous System: Organization; Function; Dysfunction Brent Fedirchuk, PhD Department of Physiology and Pathophysiology...

MPAS; PAEP7002 Autonomic Nervous System: Organization; Function; Dysfunction Brent Fedirchuk, PhD Department of Physiology and Pathophysiology Rm 410 BMSB (204) 789-3762 [email protected] All materials in this document not covered by preexisting copyright is copyright © Jan, 2025 by Brent Fedirchuk and may not be reproduced in any way without his express permission. This material is presented in this format and by this method for the benefit of the University of Manitoba MPAS 2026 Class students attending the 2025 PAEP7002 – “Physiology” course and may not be used in whole or in part for any other purpose or by another individual without the express permission of the holder of the copy and intellectual property rights.  Learning Objectives: ANS: Organization, Function, Dysfunction 1. Define homeostasis and explain the operation of a negative feedback loop that has sensor(s), a control center and effector(s). 2. Describe the structure of the sympathetic and parasympathetic divisions of the ANS. Include description of the locations of the cell bodies of preganglionic and postganglionic neurons for each division. List the cranial nerves carrying parasympathetic efferents. 3. Describe the neurotransmitters released by preganglionic and postganglionic neurons for both the sympathetic and parasympathetic divisions of the ANS, and the receptor types present on the target tissues. 4. Describe the general physiological responses to an increase in sympathetic or parasympathetic efferent outflow to the pupil, heart, stomach, skin, GI tract, male and female reproductive organs, and lower urinary tract. 5. Discuss the concept of ANS "tone", i.e. parasympathetic and sympathetic cooperation, as related to control of pupil size. Discuss sympathetic “tone” as related to skin blood flow. 6. Describe the systems involved in control of 1) continence and micturition and, 2) male sexual function. 7. Describe the normal response of the ANS to: a) sudden hypertension; b) sudden hypotension. 8. Describe 3 conditions in which there is a generalized failure of the autonomic nervous system. 9. Describe Horner’s syndrome and list four anatomical locations where a lesion could produce it. 10. Describe the hallmarks of autonomic dysreflexia, and explain why spinal cord injury at the cervical level is likely to produce it. 11. Define the “bladder/sphincter dyssynergia" relating to micturition and explain why loss of descending control produces it. 12. State why lesions in, or dementia affecting, prefrontal cortical areas can result in incontinence. 13. Define syncope and describe two common causes of it. 14. Describe: the organization of the enteric system, how the ANS regulates it, and a clinical condition arising from a congenital defect in the enteric system.  Homeostasis -from Greek: homoios = “similar” and stasis = “standing still” Definition: 1. The state of equilibrium (balance between opposing pressures) in the body with respect to various functions and to the chemical compositions of the fluids and tissues. 2. The processes through which such bodily equilibrium is maintained. Stedman’s Medical Dictionary, Electronic Ed. 2000. Homeostasis is attained through negative feedback control using: sensors, effectors & control centers.  Negative Feedback as a Regulatory Loop e.g. muscle activity, e.g. skin thermoreceptors, changes to cardiac output etc. baroreceptors etc. Negative feedback loop. An increase in the variable produces an effector response to decrease it and vice versa. Introduction, Revest, Patricia, Medical Sciences, 1, 1-14; Copyright © 2015 © Elsevier Limited Like a thermostat…. A typical “control circuit” Negative Feedback E.g. - Control of Temperature Control of body temperature by negative feedback. (A) Responses to an increase in body temperature; (B) responses to a decrease in body temperature. Introduction Revest, Patricia, Medical Sciences, 1, 1-14; Copyright © 2015 © Elsevier Limited  Automatic, not voluntary The Autonomic Nervous System – “ANS” An Overview: The ANS controls many of the organ systems of our body Often has rapid effects Maintains homeostasis in the long term sometimes called the “involuntary” or “vegetative” nervous system comprised of: o Afferents (sensory input: visceral, somatosensory, special senses) g, exiting Control Centres (central processing, e.g. centers in brainstem) -control activity in ANS and relative activation of Sympathetic vs Parasympathetic divisions Efferents (output: sympathetic, parasympathetic, enteric) Target Tissue (smooth muscle, heart tissue, glands) 3 Divisions “Sympathetic “ vs. “Parasympathetic” vs “Enteric”  Synapses, Neurotransmitters and Receptors used by ANS Target Tissue majority → exceptions → Simplified, diagrammatic representation of the anatomical and pharmacological subdivisions of the autonomic ( peripheral ) nervous system. Somatic motor neurons convey signals from the spinal cord via efferent nerves to skeletal muscles. In the CNS, the cell body of each somatic motor neuron is in the spinal cord; the neuron terminates in close proximity to the effector muscle at a specialised site, the neuromuscular junction. The neurotransmitter released by the motor efferent at the neuromuscular junction is acetylcholine and the receptor stimulated by acetylcholine is a subclass of the nicotinic receptor. Pharmacology, Wieczorek, Walter, Medical Sciences, 4, 101‐153 Copyright © 2015 Elsevier Ltd.  Sympathetic and Parasympathetic Divisions of the ANS have both similarities, and differences in their organization. Both systems: exert effects through a 2 neuron chain (usually) have a peripheral synapse (→ ganglia) =“preganglionic” and “postganglionic” neurons preganglionic neurons of both systems release ACh But: location of preganglionic soma are parasympathetic efferents in: different CN III, VII, IX and X parasympathetic preganglionics: ‐brainstem and sacral cord sympathetic preganglionics: ‐thoracic / upper lumbar spinal cord (“thoracolumbar”) ganglia in different locations postganglionic neurons release different neurotransmitters parasympathetic postganlionics: ACh sympathetic postganglionics: NE (Norepinephrine) PNS uses paracholinergic neur Pharmacology, Wieczorek, Walter, Medical Sciences, 4, 101‐153 Copyright © 2015 Elsevier Ltd.  ANS control of the Enteric Nervous System Enteric Nervous System is the neural network intrinsic to the gastrointestinal tract, and which functions to regulate GI function. -use serotonin (5-HT), dopamine (DA) and other transmitters ANS innervation of the GI Tract: parasympathetic from vagal motor nuclei (via CN X) to intestine & colon parasympathetic from sacral spinal segments to descending colon and rectum sympathetic innervation from thoracolumbar segments Sympathetic activity → decreased gut motility (and decreased digestion) Parasympathetic activity → increased gut motility (and promotes digestion) postganglionic preganglionic sensory fibres sympathetic parasympathetic longitudinal m. myenteric plexus circular m. submucosal plexus gut wall Katzung; Introduction to Autonomic Pharmacology; Fig 6.2  Small diameter myelinated and unmyelinated fibers are used by the ANS Sympathetic Parasympathetic Preganglionic in many peripheral neuropathies, the first CNS neurons fibres to be affected are small diameter unmyelinated and myelinated fibres. small myelinated therefore, diseases / conditions that affect ACh peripheral nerves (e.g. diabetes) nicotinic frequently include symptoms of ANS failure. ACh Postganglionic nicotinic PNS neurons unmyelinated NA ACh muscarinic Target tissue  Sympathetic and Parasympathetic effects on target tissues SNS (catabolic) PNS (anabolic) 1. Heart action receptor action receptor Sinoatrial Node β1 muscarinic Contractility β1 muscarinic 2. Vascular Smooth Muscle Skin, Gut contract α not innervated Skeletal & Coronary relax/contract β2/α not innervated 3. Gastro-Intestinal Smooth Muscle Walls relax β2 contract muscarinic Sphincters contract α relax muscarinic Secretion α muscarinic α β1 & β2 are adrenergic receptors  Sympathetic and Parasympathetic effects on target tissues (cont’d) SNS (catabolic) PNS (anabolic) 4. Bladder action receptor action receptor sor muscle Wall relax β2 contract muscarinic Neck (Sphincter) contract α relax muscarinic 5. Airway Bronchiole Smooth Muscle relax β2 contract muscarinic secretions muscarinic 6. Pupil mydriasis α miosis muscarinic (dilation) (constriction)  Sympathetic and Parasympathetic effects on target tissues (cont’d) SNS (catabolic) PNS (anabolic) action receptor action receptor 7. Sweat Glands sweating muscarinic not innervated 8. Sex Organs Female uterine α not innervated contraction Male ejaculation α erection complex (e.g. NO) Target Tissues SNS Action SNS Receptor PNS Action PNS Receptor Heart SA node increases β1 decreases M Heart Contractility increases β1 decreases M Vascular SM: Skin, Gut contract α Vascular SM: Skeletal, Relax/contract β2/α Coronary GI SM: Walls relax β2 contract M GI SM: Sphincters contract α relax M GI SM: Secretion decreases α increases M Bladder Wall relax β2 contract M Bladder Neck (sphincter) contract α relax M Airway Bronchiole SM relax β2 contract M ↑secretions Pupil Mydriasis α Miosis M (Dilation) (constriction) Sweat glands sweating M Female sex organs Uterine α contraction Male sex organs Ejaculation α Erection complex  Summary of Sympathetic vs Parasympathetic Div’s Sympathetic Division: -Preganglionic neurons with soma in intermediolateral cell column of thoracolumbar spinal cord. -Preganglionic neurons release ACh → Postganglionic neurons (nicotinic receptors; paravertebral, prevertebral ganglia) -Postganglionic neurons usually release NE at target tissue. -Sympathetic effects usually mediated by α1, α2, β1, β2 adrenergic receptor types. → effects that serve to mobilize energy and prepare the body for activity… “catabolic” (= fight or flight type responses) Parasympathetic Division: -Preganglionic neurons with soma either in brainstem, or sacral intermediolateral cell column. -Preganglionic neurons release ACh → Postganglionic neurons (nicotinic receptors; ganglia near target tissue). -Postganglionic neurons release ACh at target tissue. -Parasympathetic effects mediated by muscarinic ACh receptors. → effects that decrease energy consumption, and replenishes & restores the body’s stores of energy. “anabolic” responses  Autonomic control of Pupil Size Parasympathetic → constriction (miosis) via Sphincter pupillae m. ‐from midbrain Edinger Westphal n. (CN 3) Sympathetic → dilation (mydriasis) via Dilator iridis m. only Parasympathetic balance of Parasympathetic & Sympathetic only Sympathetic Pupil diameter is result of relative activity of parasympathetic and sympathetic systems  Pupillary Light Reflex Light entering one eye: 1. activates retinal cells, information is transmitted via one optic nerve and bilaterally activates the parasympathetic Edinger‐ Westphal nuclei in the midbrain. 2. preganglionic parasympathetic neurons in the E‐W nuclei project to the ciliary ganglia; postganglionic parasympathetic neurons travelling along CN3 (oculomotor) → constriction of pupils 3. consensual reflex response (both pupils constrict) Blumenfeld, Neuroanatomy through clinical cases, 2010, Fig. 13.2; 13.8 ANS control of Bladder and Reproductive Organs: Review ANS Anatomy sympathetic parasympathetic modified from  Autonomic control of Male Sexual Function Peripheral sensory or psychogenic initiation of two phase response: 1) erection via parasympathetics, 2) ejaculation via sympathetics, accompanied with rhythmic Descending influences contraction of striated muscles at base of the penis (controlled by pudendal somatic motoneurons) Bladder Sympathetic Thoraco- chain lumbar spinal cord Glans Dorsal penile n. Urethra Hypogastric n. (sympathetic) Ischio- and bulbo- Erectile tissue cavernosus mm. Vas deferens Pelvic n. (parasympathetic) Epididymis Testis Sacral spinal cord Pudendal n. (somatic) Autonomic control of the Urinary Bladder Parasympathetic innervation: -from neurons in the sacral intermediolateral cell column. -causes bladder contraction (activated for micturition) Sympathetic innervation: -from neurons in the thoracic intermediolateral cell column. -causes relaxation of the bladder, and contraction fo the bladder neck and proximal urethera (smooth muscle). -works with somatic motor system to maintain continence. Micturition (bladder emptying): Bladder stretch receptors provide sensory information on the state of the bladder. Higher (brain) centers send a descending command that causes activation of the parasympathetic system and a decrease in activity in somatic and sympathetic systems that had been maintaining urinary continence. Disruption of this descending pathway (e.g. spinal cord injury) can result in: “Bladder / Sphincter Dyssynergia”.  Sympathetic -relax smooth muscle of bladder body -contract smooth muscle of bladder neck ‐ →CONTINENCE Bladder Parasympathetic + detrusor (body) -contract smooth muscle of the bladder body →MICTURITION + Bladder neck Somatic pudendal Urethra motoneurons - innervate the pelvic floor + & external urethral striated Pelvic floor External sphincter muscles striated muscles - when active, assist in Sphincter muscle →CONTINENCE  Bladder and sphincter Cerebellum Frontal Basal reflex pathways during micturition Cortex ganglia BRAINSTEM 1. Bladder distension is sensed and primary sensory afferents carry info about fullness to the CNS. 2. Brainstem “micturition centre” processes the information -- if appropriate, frontal cortex switches the “pontine micturition centre” from continence → Thoraco- micturition mode. lumbar 3. Descending pathways from the brainstem help to Hy pogas tric n. turn off the sympathetics, turn on the sacral Ascending parasympathetics and inhibit the pudendal tracts motoneuron output to the sphincter/pelvic floor muscles - and they relax. Pelvic afferent Bladder Pelvic ganglia Sacral Bladder contracts, Urethral sphincter relaxes Urethra → bladder emptying Pudendal n. External urethral sphincter muscle  ANS Responses to Low Blood Pressure “Baroreceptor Reflex” Blood Pressure High 4 The typical AP Normal Low Blood Pressure Baroreceptor Low E.g. change to upright posture afferents ond span, so it 1 sed 5 1. Baroreceptors detect LOW BP - Signals via CN 9 and 10 decrease. 2 2. Brainstem cardiovascular centre assesses the drop in signal and sends signals to inhibit Vagal parasympathetics (increases heart rate & contractility) 3. Also, descending reticulospinal systems send message to EXCITE thoracolumbar 3 Sympathetics - excite the heart & excite sympathetic constriction More SN of blood vessels (increase peripheral blood ve resistance). 4 4. With increased cardiac output and Periphe peripheral resistance, BP goes up. (PVR) is 5. Increase BP sensed and signals now adjusted to keep the new desired blood pressure. ANS Responses to Blood Pressure Changes The “Baroreceptor Reflex” High blood pressure Low blood pressure Blood Pressure Blood Pressure Normal High Low Normal carotid & aortic arch baroreceptors Fedirchuk 2023  Blood vessels in the skin are controlled only by sympathetic innervation Increase sympathetic output → Vasoconstriction Decrease sympathetic output → Vasodilation “peripheral resistance” to blood flow has a dramatic effect on blood pressure vasoconstriction → increased blood pressure vasodilation → lowering of blood pressure represents blood vessel diameter “sympathetic tone” determines peripheral resistance 5 minute break  Autonomic Failure Symptoms of Sympathetic failure: cardiovascular: postural hypotension, syncope skin: no sweating (→ heat intolerance), no flare when scratched eye: Horner’s syndrome Symptoms of Parasympathetic failure: dry mouth, eyes (↓ secretions) blurred vision (↓ accommodation) impotence poor GI motility bladder dysfunction (↓ bladder contraction) Causes of Autonomic Failure: 1. pharmacologic: intentional (therapeutic); drug overdose; poisoning 2. peripheral neuropathy: e.g. diabetes; Guillain‐Barré syndrome (acute neuropathy) 3. CNS degeneration; multiple systems atrophy 4. CNS site‐specific lesions affecting portions of the ANS 5. genetic (several types, rare)  Horner’s syndrome: indicative of loss of sympathetic innervation of the eye 6. lid, pupil, blood vessels Parasympathetic → constriction (miosis) via Sphincter 5. along CN III. pupillae m. (from midbrain Edigner Westphal n. (CN 3) Sympathetic → dilation (mydriasis) via Dilator iridis m., CN V (also innervates superior tarsal m., contributes to eyelid opening) only Parasympathetic balance of Parasympathetic & Sympathetic 1.start in hypothalamus only Sympathetic 4. along carotid a. 3. sup. cervical gang. 2.5 Cervical sympathetic pathway. Loss of Sympathetic innervation of the eye: A lesion anywhere along the sympathetic 2.brainstem to thoracic cord pathway results in: he pupil i. a small pupil ii. slight drooping of the eyelid (ptosis) Fig 2.6 iii. a bloodshot eye all on the same side as the lesion. Collectively: Horner’s syndrome from Patten, “Neurological Differential Diagnosis” ANS Responses to Blood Pressure Changes The “Baroreceptor Reflex” High blood pressure Low blood pressure Blood Pressure Blood Pressure Normal High Low Normal carotid & aortic arch baroreceptors Fedirchuk 2023  Autonomic dysreflexia in spinal cord injury (1) High spinal cord lesions remove reticulospinal control of the Sympathetic system, and can allow Autonomic dysreflexia to Autonomic Dysreflexia occur. A high lesion (Lesion A, above T1): Brainstem ‐leaves the entire sympathetic chain without IX CV centres descending control X ‐afferent input can → sympathetic activity ‐ ↑ BP (often dramatically) baroreceptors ‐Heart slowed by vagal parasympathetics Blood (dangerous bradycardia) vessel Lesion A Heart T1 Quadraplegia (quadriplegic it Paradox: Dangerously high BP, with dangerously slow HR ‐can be a variety of afferent triggers (e.g. bladder, bowel, cutaneous, infection etc) Blood L1 vessels Autonomic dysreflexia is a medical emergency. Treatment: 1. remove the stimulus Afferent ‐e.g. drain bladder, lidocaine on skin lesion etc trigger 2. ganglion blockers (e.g. nicotinic ACh antagonists) Skin: (bedsores) Uterus: (labour and delivery) ‐stops sympathetic output/drive Bladder: (overdistended) Interstine: (impacted) Other?  Brainstem control of Sympathetic system is lost after spinal cord injury Reticulospinal system Disrupted Reticulospinal system limits BP increase cannot inhibit sympathetic activity X Nociceptor signal activates spinal sympathetic Nociceptor signal activates spinal sympathetic preganglionics preganglionics increased BP sensed by baroreceptors increased BP sensed by baroreceptors CV control centre in medulla CV control centre in medulla ‐activates parasympathetic system (slows heart) ‐activates parasympathetic system (slows heart) ‐inhibits sympathetic system (limits BP increase) ‐SCI disrupts descending system that inhibits sympathetic system (vasoconstriction cannot be inhibited → persistent BP increase) McCrea 2015  Autonomic dysreflexia in spinal cord injury (2) High spinal cord lesions remove reticulospinal Autonomic Dysreflexia control of the Sympathetic system, and can allow Brainstem Autonomic dysreflexia to occur. IX CV centres X baroreceptors Blood vessel Heart T1 With a lower spinal cord lesion (e.g. Lesion B) ‐only the portion of the sympathetic system below the lesion is unregulated Lesion B Blood Paraplegia L1 (paraplegic vessels ‐there is a lesser likelihood of autonomic dysreflexia, and if it occurs, it is less severe Afferent trigger Skin: (bedsores) Uterus: (labour and delivery) Bladder: (overdistended) Interstine: (impacted) Other?  ANS Responses to Low Blood Pressure Low blood pressure Blood Pressure to avoid fainting when standing: Low Normal baroreceptor afferents signal carotid & aortic arch baroreceptors decreased BP (vagus n.) brain reduces parasympathetic activity descending pathway activates sympathetic system (spinal) sympathetic system constricts blood vessels (↑ BP), and ↑ heart rate “Baroreceptor Reflex” Fedirchuk 2023  Syncope fainting (syncope) = a brief loss of consciousness accompanied by loss of postural tone, and with a spontaneous recovery. Presyncope is the feeling of light‐headedness, the anticipation of fainting. caused by insufficient blood flow to the brain as a result of: hypovolemia cardiovascular system failing to maintain adequate blood pressure & perfusion. failure of the ANS to regulate blood flow to the brain. cardiogenic syncope (arrhythmia, obstruction, low BP)  Syncope (2) Orthostatic (postural) hypotension typically when going from lying or sitting to standing. failure of ANS to activate vasomotor system and heart to increase BP and heart rate can be caused by: drugs (e.g. α1 blockers, and others) CNS degeneration (e.g. multiple system atrophy) neuropathy of autonomic efferents (e.g. diabetes) hypovolemia Neurogenic syncope (or vasovagal syncope) Failure of the ANS to adequately regulate blood flow to the brain. (Term vasovagal may be inaccurate as it implies an underlying parasympathetic mechanism, but syncope can also result from ↓ sympathetic tone.) trigger (e.g. emotion, pain, sight of blood, etc.) shuts down the ANS briefly. maybe from unusual activation of vagus nerve (→ slows heart, ↓ sympathetic tone) straining during defecation or urination can → strong parasympathetic activation (↓ heart rate) and concomitant ↓ sympathetic tone (↓ BP). micturition syncope (may also occur after micturition). Likely b/c ↓ sympathetic tone after micturition, and therefore ↓ BP. Autonomic control of the Urinary Bladder Parasympathetic innervation: -from neurons in the sacral intermediolateral cell column. -causes bladder contraction (activated for micturition) Sympathetic innervation: -from neurons in the thoracic intermediolateral cell column. -causes relaxation of the bladder, and contraction fo the bladder neck and proximal urethera (smooth muscle). -works with somatic motor system to maintain continence. Micturition (bladder emptying): Bladder stretch receptors provide sensory information on the state of the bladder. Higher (brain) centers send a descending command that causes activation of the parasympathetic system and a decrease in activity in somatic and sympathetic systems that had been maintaining urinary continence. Disruption of this descending pathway (e.g. spinal cord injury) can result in: “Bladder / Sphincter Dyssynergia”.  Sympathetic -relax smooth muscle of bladder body -contract smooth muscle of bladder neck ‐ →CONTINENCE Bladder Parasympathetic + detrusor (body) -contract smooth muscle of the bladder body →MICTURITION + Bladder neck Somatic pudendal Urethra motoneurons - innervate the pelvic floor + & external urethral striated Pelvic floor External sphincter muscles striated muscles - when active, assist in Sphincter muscle →CONTINENCE  Bladder and sphincter Cerebellum Frontal Basal reflex pathways during micturition Cortex ganglia BRAINSTEM 1. Bladder distension is sensed and primary sensory afferents carry info about fullness to the CNS. 2. Brainstem “micturition centre” processes the information -- if appropriate, frontal cortex switches the “pontine micturition centre” from continence → Thoraco- micturition mode. lumbar 3. Descending pathways from the brainstem help to Hy pogas tric n. turn off the sympathetics, turn on the sacral Ascending parasympathetics and inhibit the pudendal tracts motoneuron output to the sphincter/pelvic floor muscles - and they relax. Pelvic afferent Bladder Pelvic ganglia Sacral Bladder contracts, Urethral sphincter relaxes Urethra → bladder emptying Pudendal n. External urethral sphincter muscle  Compromised Bladder Control 1. dementia and frontal cortex lesions can → incontinence the frontal cortex is needed for the decision process of when it is appropriate to void (i.e. when to inhibit the somatic sphincter muscles) 2. Loss of brainstem control of spinal micturition networks in the sacral spinal cord often → bowel and bladder dysfunction. (e.g.’s Spinal cord injury, MS affecting descending systems) with damage to descending control systems, spinal bladder reflexes → bladder contraction as if fills (=“spastic bladder”), but little urine flows. There is a failure to inhibit the somatic external urethral sphincter motoneurons, so the bladder contracts against a high outlet resistance. bladder contraction with failure to relax urethral sphincter = bladder / sphincter dyssynergia would cause incomplete bladder emptying (residual urine) and require intermittent self‐ catheterization. the urinary retention, and repeated catheterization both lead to urinary tract infections being a common problem after spinal cord injury.  Compromised Bladder Control (2) 3. damage to sacral spinal efferents / afferents: E.g.’s ‐ damage to sacral spinal cord, or masses compressing the sacral cord or cauda equina region ‐damage to pelvic nerves ‐can damage ANS control, and/or ANS fibres going to the bladder ‐can result in a flaccid bladder (urinary retention) or incontinence (reduced sphincter tone).  ANS control of the Enteric Nervous System Enteric Nervous System is the neural network intrinsic to the gastrointestinal tract, and which functions to regulate GI function. -use serotonin (5-HT), dopamine (DA) and other transmitters ANS innervation of the GI Tract: parasympathetic from vagal motor nuclei (via CN X) to intestine & colon parasympathetic from sacral spinal segments to descending colon and rectum sympathetic innervation from thoracolumbar segments Sympathetic activity → decreased gut motility (and decreased digestion) Parasympathetic activity → increased gut motility (and promotes digestion) postganglionic preganglionic sensory fibres sympathetic parasympathetic longitudinal m. myenteric plexus circular m. submucosal plexus gut wall Katzung; Introduction to Autonomic Pharmacology; Fig 6.2  Congenital Megacolon Congenital aganglionic megacolon (Hirschsprung’s disease): parasympathetic innervation developmental failure of cells to migrate and form neural networks enteric plexus (Auerbach’s and Meissner’s plexus) in sections of the large intestine (colon). Proximal Distal sections without parasympathetic innervation constrict (→ “pseudosphincter”), causing fecal sympathetic postganglionic axons matter to accumulate proximally. manifests in newborns, as their GI tract starts using peristalsis enteric plexus severity of symptoms (constipation, bowel distention) depends on the Proximal Megacolon Distal length of colon not properly innervated usually good prognosis following surgery. sympathetic postganglionic axons  ANS: Organization, Function, Dysfunction ‐ Self Study Questions 1 1. An 18 year old male quadriplegic (2 years post injury) came to the emergency department with the complaint of a sudden onset, severe, throbbing, headache. Except for the spinal injury, he had been previously healthy with no history of falls or loss of consciousness. Neurological examination is unremarkable. His heart rate was slow at 40 beats per minute and his blood pressure high at 220 /170 mmHg. His bladder was palpated and found to be distended; 600 cc of fluid was drained via a trans-urethral catheter. His heart rate and blood pressure did not change. Further examination revealed a 2 cm inflamed and infected compression sore on his left buttock. i. What produced the elevated blood pressure? What pathways are involved? ii. What produced the bradycardia? What pathways are involved? iii. What actions should be taken to alleviate this acute cardiovascular crisis? iv. What is the likely cause of this patient’s distended bladder? How is this problem normally managed in spinal cord injured individuals? 2. A 58 year old man presents with a left pupil that is smaller than his right pupil, a left eyelid that droops slightly and he has a bloodshot left eye. He has also noticed that he does not sweat on the left side of his face, the left side of his chest, or left arm. i. Explain each of his left eye symptoms in terms of altered function in the autonomic nervous system. ii. Outline the course of the pathway for sympathetic control of the eye. iii. Why does he have altered sweating on the left side? ANS: Organization, Function, Dysfunction ‐ Self Study Questions 2 3. A 75-year-old man lost consciousness briefly in his bathroom. Shortly after walking to the bathroom to urinate, he became light-headed, his vision went “funny” and the next thing he knew he was lying awake on his bathroom floor. His wife notes that he was unconscious only briefly. He was able to give a clear account of what happened soon after the incident. Clinical examination finds him alert with excellent mental status, good gait, HR 65, BP 135/80, no ECG abnormalities and with no signs of cranial nerve dysfunction. i. Do you think this represents orthostatic hypotension, or a different type of syncope? Explain your rationale. 4. A newborn fails to pass its first stool (meconium) for four days after birth (normally 1-2 days). The baby has a distended abdomen and appears in distress. The pediatrician is concerned about the possibility of a defect in the peristaltic ability of the GI tract. A rectal barium deposit and X-ray reveals a constricted area of the lower bowel close to the anus. i. Describe the innervation of the gut that propels food through the digestive system. ii. Describe the roles of the Sympathetic and Parasympathetic divisions of the ANS in regulating the enteric system. iii. Name a genetic disorder that can have this presentation and describe the pathophysiology.