In addition to the resource cited in this post please see Links To And Excerpts From “Autonomic Nervous System Dysfunction: JACC Focus Seminar”
Posted on February 13, 2022 by Tom Wade MD
In this post, I link to and excerpt from Autonomic Dysfunction by StatPearls. Last Update: November 21, 2021.
All that follows is from the above resource.
Introduction
The autonomic nervous system (ANS) is a subcomponent of the peripheral nervous system (PNS) that regulates involuntary physiologic processes, including blood pressure, heart rate, respiration, digestion, and sexual arousal. It comprises sympathetic, parasympathetic, and enteric nervous systems, which are three anatomically distinct divisions. The sympathetic nervous system (SNS), as well as the parasympathetic nervous system (PNS), contain afferent fibers that provide sensory input and efferent fibers that provide motor output to the central nervous system (CNS). The SNS and PNS motor pathways incorporate a two-neuron series: a pre-ganglionic neuron with a cell body in the CNS and a post-ganglionic neuron with a cell body in the periphery that innervates target tissues[1]. The enteric nervous system (ENS) is a large, web-like structure capable of functioning independently of the remainder of the nervous system.[2][3] It is chiefly responsible for regulating digestive processes and contains over a hundred million neurons of over fifteen morphologies, greater than the sum of all other peripheral ganglia.[4][5]
The autonomic nervous system (ANS) includes all regions implicated in controlling “autonomic,” unconscious, and involuntary functions in total body homeostasis. In general, the full range of physiologic functions are ultimately necessary for human survival and allow us to interact with the external environment in a wide range of conditions. Together with the slow-acting, long-lasting effects of the endocrine system, the ANS exerts its fast-acting, short-lived effects on the following functions (among others):
Perfusion of the whole body through regulation of heart rate and blood pressure Homoeothermic role through sweating control and shivering, Processing of nutrients through control and coordination of different parts of the gut and glands, Urinary motility, and Pupil movement, focusing, and lacrimation.Table 1. Autonomic nervous system functions[3]
Organ Sympathetic activation Parasympathetic activation Eye Ciliary muscle
Pupils
Relax (far vision)
Dilation (dilator muscle)
Constrict (near vision)
Constriction (sphincter muscle)
Lacrimal gland Salivary glands
Slight secretion Slight secretion
Secretion Secretion
Heart Contractility (muscle)
Rate (sinus node)
Increase
Increase
Decreased or none
Decrease
Lungs Bronchodilation Bronchoconstriction Gastrointestinal tract Decrease motility Increase motility Kidney Antidiuresis (decreased output) None Urinary bladder Detrusor muscle
Sphincter
Relaxation
Contraction
Contraction
Relaxation
Penis Ejaculation Erection Clitoris, labia minora None Swelling/ Erection Nipples None Erection Sweat glands Secretion Palmar sweating Piloerector muscles Contraction None Blood vessels Large arteries
Arterioles
Precapillary sphincters
Venules
Large veins
Coronary arteries
Constriction
Constriction
Constriction
Constriction
Constriction, volume mobilization
Dilatation
None
None
None
None
None
None
Muscle Muscle spindles
Arterioles
Metabolism
Decreased sensitivity
Dilatation
Increased
None
None
NOne
Liver Glycolysis, glucose mobilization Glycogen synthesis Fat tissue Lipolysis None Immune system Suppressed Activated From: Autonomic Dysfunction
Dysfunction of one or more subdivisions of the ANS, when accompanying other diseases, is linked to a worse prognosis of the latter. In some circumstances or when severe, dysfunction of ANS itself results in symptoms and disability, which may, in turn, prompt treatment.[6][7][8][9][10]
Etiology
A myriad of the factors can cause autonomic dysfunction, and more than one can concur even in the same patient. Due to the expansive nature of the autonomic nervous system, it can be affected by a wide range of conditions[11][12][13]. The most common factors known to cause autonomic dysfunction include the following:
Inherited
Amyloidosis, Fabry disease, hereditary sensory autonomic neuropathy, porphyrias Genetic disorders like familial dysautonomia and dopamine-beta-hydroxylase deficiencyAcquired
Autoimmune: Guillain-Barre, Autoimmune autonomic ganglionopathy, Lambert-Eaton myasthenic syndrome, rheumatoid arthritis, Sjogren, systemic lupus erythematosus Abnormal reflex responses in carotid sinus hypersensitivity, vasovagal syncope, and other neuro-meditated syncopes; and probably in postural tachycardia syndrome (PoTS) Abnormal sweating responses, as in generalized or focal hyperhidrosis, are related to excessive activation. Metabolic/ Nutritional: Diabetes mellitus, vitamin B12 deficiency Degenerative neurologic diseases: Parkinson disease, multiple system atrophy/Shy-Drager syndrome, pure autonomic failure presenting or suffering from orthostatic hypotension, fixed heart rate responses Infections: Botulism, Chagas disease, human immunodeficiency virus (HIV), leprosy, Lyme disease, tetanus Neoplasia: Brain tumors, paraneoplastic syndromes Pharmacologic effects of several drugs that interfere with normal autonomic function and provoke symptoms include alpha- and beta-blocker-triggered orthostatic hypotension Toxin/drug-induced: Alcohol, amiodarone, chemotherapy Traumatic or tumoral spinal cord injuries at different levels and presenting with the so-called autonomic dysreflexia Uremic neuropathy/chronic liver diseasesMedications That Exacerbate Orthostatic Hypotension
Diuretics: furosemide, torsemide, thiazide Nitric oxide-mediated vasodilators: nitroglycerine, hydralazine, sildenafil Adrenergic antagonists:
Alpha-1-adrenergic blockers: alfuzosin, terazosin Beta-adrenergic blockers: propranolol Alpha -2-adrenergic agonists: tizanidine, clonidine Renin-angiotensin system inhibitors: lisinopril, valsartan Dopamine antagonists:
Phenothiazines: chlorpromazine Atypical antipsychotics: olanzapine, risperidone, quetiapine Calcium channel blockers: verapamil, diltiazem Selective serotonin receptor reuptake inhibitors: paroxetine Antidepressants: trazodone, amitriptylineEpidemiology
Autonomic dysfunction, taken as a whole, is not infrequent. The most common autonomic dysfunction occurs in the cardiovascular control sphere and consists of an abnormal vasovagal response that leads to syncope. Other common manifestations are related to postural tachycardia syndrome (POTS) or changes seen with Parkinson disease and other parkinsonisms. Compared to other areas of autonomic control, urinary incontinence, as observed in multiple sclerosis and other nervous system disorders, is unspecific but not rare. Some symptoms of autonomic disturbance, such as the facial vasomotor and ocular symptoms in trigeminal autonomic headaches, are of secondary significance but help in diagnosis.[14][15][16][17]
Orthostatic hypotension occurs in patients with neurodegenerative disorders such as Parkinson disease, multiple system atrophy, pure autonomic failure, and in individuals with ganglionopathies that affect autonomic nerves and peripheral neuropathy. The prevalence of orthostatic hypotension is proportional to age, and it is more common in institutionalized than community-dwelling elderly[18]. POTS is more prevalent in women. Syncope is highly prevalent in the general population, and the majority of syncope is due to reflex syncope. The frequency of reflex syncope is higher during adolescence and in individuals over 55 years. Carotid sinus hypersensitivity, defecation, and cough syncope occur almost exclusively in the elderly population.[18]
Pathophysiology
Pathophysiology in ANS depends upon the affected area. Both anatomically related, as well as isolated regions, can be affected. In the cardiovascular system, three pathophysiological syndromes are typically associated with chronic dysfunction of the ANS. These are Postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension with supine hypertension, and reflex cardiovascular syndromes. Hyperhidrosis and hypohidrosis are the main features of temperature control. Fixed mydriasis and myosis, also known as Adie’s pupil and Horner syndrome in the eye, are also seen.
Autonomic dysfunction may result from any disease that affects the peripheral or central components of ANS. Primary autonomic dysfunction involves primary (idiopathic) degeneration of autonomic postganglionic fibers without other neurologic abnormalities.
Orthostatic hypotension is defined as a sustained reduction of systolic blood pressure of at least 20 mmHg or diastolic blood pressure of 10 mmHg within three minutes of standing or head-up tilt to at least 60 degrees on the tilt table. The magnitude of fall in blood pressure depends on baseline blood pressure. In patients with supine hypertension, a reduction of 30 mmHg in systolic blood pressure may be an appropriate criterion for orthostatic hypotension.
Neurally mediated (reflex) syncope includes vasovagal, carotid sinus, situational (cough, swallowing, micturition) syncope. It refers to a diverse group of conditions in which there is a relatively sudden change in ANS activity leading to a drop in blood pressure, heart rate, and cerebral perfusion. Neurally mediated syncope is best understood as a reflex with afferent, central, and efferent pathways, and the use of ‘neurocardiogenic syncope’ should be abandoned because the origin of the reflex is rarely in the heart.
Postural tachycardia syndrome (POTS) is defined as a sustained heart rate increment of 30 beats per minute within 10 minutes of standing or head-up tilt in the absence of orthostatic hypotension. For individuals of ages 12 to 19 years, the requirement is at least 40 beats per minute. POTS may be accompanied by symptoms of autonomic overactivity and cerebral hypoperfusion that are relieved by recumbency. The pathophysiology and etiology of POTS are unknown but are likely heterogeneous. POTS is associated with recent viral illness, chronic fatigue syndrome, deconditioning, and limited or restricted autonomic neuropathy.[18]
Diabetic neuropathy is a kind of nerve pathology that may occur for those with diabetes mellitus. Hyperglycemia interferes with a nerve’s ability to send signals and weakens the walls of the vasa nervorum blood vessels that supply nerves with nutrients and oxygen. Diabetic neuropathy can affect the nerves of the ANS, especially general visceral afferent (GVA) fibers, resulting in gastroparesis and decreased blood pressure regulation.[20] GVA fibers affected by diabetic neuropathy reduce the response of their corresponding general visceral efferent (GVE).
Parkinson disease is a progressive neurodegenerative disease characterized by bradykinesia and hypokinesia combined with rest tremor and rigidity. Constipation, dysphagia, sialorrhea, rhinorrhea, urinary difficulties, and sexual dysfunction are the common nonmotor problems related to autonomic dysfunction in Parkinson disease.[21]
History and Physical
A detailed account of symptoms in each area should guide us to list possible diseases with autonomic dysfunction. Emphasis should be placed on obtaining a good history and comprehensive examination of cardiovascular, urinary, neurological, and sudomotor manifestations. A key feature of autonomic dysfunction, either orthostatic syncope or presyncope, should guide us to suspicion of cardiovascular autonomic dysfunction. In this scenario, the usual orthostatic symptoms consist of lightheadedness, visual blurring or tunnel vision, neckache (coat-hanger pain), nausea, palpitations, tremulousness, weakness, and dizziness. Other symptoms include exercise intolerance, fatigue, shortness of breath, chest pain, anxiety, hyperventilation, acral coldness or pain, concentration difficulty, and headaches.[18] The alternating sweating intensity in different areas of the body, typically a length-dependent distal hypohidrosis with sparing of palms and soles, can raise suspicion for a sudomotor autonomic lesion. Urgency and incontinence tend to relate to a neurogenic bladder more than retention.
Evaluation
Testing the most disturbing or salient features of autonomic dysfunction is often necessary to confirm a diagnosis and give objective evidence supporting pharmacologic treatment.[23][24][25]
Bedside evaluation of the ANS consists primarily of observing cardiovascular reflexes, casual sweating patterns, and pupillary changes.[19] Bedside tests such as orthostatic blood pressure measurement and heart rate (while supine and after three minutes standing) are the most commonly used tests. When the bedside tests are not informative, but suspicion of an abnormal cardiovascular autonomic function is high, tilt table tests with natural cardiovascular stimuli such as Valsalva maneuver, hyperventilation, or cold pressor, are needed.
Other tests are not as useful in changing the management but may play a role in supporting an explanation for the patient’s symptoms or as adjunctive for syndromic diagnosis. Blocking eyedrop tests and pupillometry for pupillary abnormalities are examples of such tests.
Some tests do help in management. For example, positive testing for autoantibodies, antibodies against alfa-3-acetylcholine receptors helps support immunosuppressive therapy.
Indications of Tilt Table Test[26]:
High suspicion of orthostatic hypotension despite an initial negative evaluation (for example, Parkinson disease).[27] Patients who have a significant motor impairment that precludes them from having standing vital signs obtained.[27] Monitor the span of an autonomic disorder and its response to therapy.[28]Responses to Head-Up Tilt-Table testing[29]:
Normal Heart rate increases by 10 to 15 beats per minute Diastolic blood pressure increases by 10 mm Hg or more
Dysautonomia Immediate and continuing drop in systolic and diastolic blood pressure No compensatory increase in heart rate
Neurogenic syncope Symptomatic, sudden drop in blood pressure Simultaneous bradycardia
Occurs after 10 minutes or more of testing
Orthostatic hypotension Systolic blood pressure decreases by 20 mm Hg or more or
Diastolic blood pressure decreases by 10 mm Hg or more
Postural orthostatic tachycardia syndrome Heart rate increases by at least 30 beats per minute or
Persistent tachycardia of more than 120 beats per minute
From: Autonomic Dysfunction
See the section, Treatment / Management [Link is to this section of the article] for detailed guidance on treatment.