The autonomic nervous system (ANS) innervates the entire neuraxis and influences all organ systems. It regulates blood pressure (BP), heart rate, sleep, and bladder and bowel function. It operates automatically; its full importance becomes recognized only when ANS function is compromised, resulting in dysautonomia. Hypothalamic disorders that cause disturbances in homeostasis are discussed in Chap. 23.

The activity of the ANS is regulated by central neurons responsive to diverse afferent inputs. After central integration of afferent information, autonomic outflow is adjusted to permit the functioning of the major organ systems in accordance with the needs of the whole organism. Connections between the cerebral cortex and the autonomic centers in the brainstem coordinate autonomic outflow with higher mental functions.

The preganglionic neurons of the parasympathetic nervous system leave the central nervous system (CNS) in the third, seventh, ninth, and tenth cranial nerves as well as the second and third sacral nerves, while the preganglionic neurons of the sympathetic nervous system exit the spinal cord between the first thoracic and the second lumbar segments (Fig. 41-1). These are thinly myelinated. The postganglionic neurons, located in ganglia outside the CNS, give rise to the postganglionic unmyelinated autonomic nerves that innervate organs and tissues throughout the body. Responses to sympathetic and parasympathetic stimulation are frequently antagonistic (Table 41-1), reflecting highly coordinated interactions within the CNS; the resultant changes in parasympathetic and sympathetic activity provide more precise control of autonomic responses than could be achieved by the modulation of a single system.

Acetylcholine (ACh) is the preganglionic neurotransmitter for both divisions of the ANS as well as the postganglionic neurotransmitter of the parasympathetic neurons; the preganglionic receptors are nicotinic, and the postganglionic are muscarinic in type. Norepinephrine (NE) is the neurotransmitter of the postganglionic sympathetic neurons, except for cholinergic neurons innervating the eccrine sweat glands.

CLASSIFICATION

Disorders of the ANS may result from pathology of either the CNS or the peripheral nervous system (PNS) (Table 41-2). Signs and symptoms may result from interruption of the afferent limb, CNS processing centers, or efferent limb of reflex arcs controlling autonomic responses. For example, a lesion of the medulla produced by a posterior fossa tumor can impair BP responses to postural changes and result in orthostatic hypotension (OH). OH can also be caused by lesions of the spinal cord or peripheral vasomotor nerve fibers (e.g., diabetic autonomic neuropathy). Lesions of the efferent limb cause the most consistent and severe OH. The site of reflex interruption is usually established by the clinical context in which the dysautonomia arises, combined with judicious use of ANS testing and neuroimaging studies. The presence or absence of CNS signs, association with sensory or motor polyneuropathy, medical illnesses, medication use, and family history are often important considerations. Some syndromes do not fit easily into any classification scheme.

SYMPTOMS OF AUTONOMIC DYSFUNCTION

Clinical manifestations can result from loss of function, overactivity, or dysregulation of autonomic circuits. Disorders of autonomic function should be considered in patients with unexplained OH, syncope, sleep dysfunction, altered sweating (hyperhidrosis or hypohidrosis), impotence, constipation or other gastrointestinal symptoms (bloating, nausea, vomiting of old food, diarrhea), or bladder disorders (urinary frequency, hesitancy, or incontinence). Symptoms may be widespread or regional in distribution. An autonomic history focuses on systemic functions (BP, heart rate, sleep, fever, sweating) and involvement of individual organ systems (pupils, bowel, bladder, sexual function). The autonomic symptom profile is a self-report questionnaire that can be used for formal assessment. It is also important to recognize the modulating effects of age. For example, OH typically produces lightheadedness in the young, whereas cognitive slowing is more common in the elderly. Specific symptoms of orthostatic intolerance are diverse (Table 41-3). Autonomic symptoms may vary dramatically, reflecting the dynamic nature of autonomic control over homeostatic function. For example, OH might be manifest only in the early morning, following a meal, with exercise, or with raised ambient temperature, depending on the regional vascular bed affected by the dysautonomia.

Early symptoms may be overlooked. Impotence, although not specific for autonomic failure, often heralds autonomic failure in men and may precede other symptoms by years. A decrease in the frequency of spontaneous early morning erections may occur months before loss of nocturnal penile tumescence and development of total impotence. Bladder dysfunction may appear early in men and women, particularly in those with a CNS etiology. Cold feet may indicate increased peripheral vasomotor constriction. Brain and spinal cord disease above the level of the lumbar spine results first in urinary frequency and small bladder volumes and eventually in incontinence (upper motor neuron or spastic bladder). By contrast, PNS disease of autonomic nerve fibers results in large bladder volumes, urinary frequency, and overflow incontinence (lower motor neuron flaccid bladder). Measurement of bladder volume (postvoid residual) is a useful bedside test for distinguishing between upper and lower motor neuron bladder dysfunction in the early stages of dysautonomia. Gastrointestinal autonomic dysfunction typically presents as severe constipation. Diarrhea may develop (typically in diabetes mellitus) due to rapid transit of contents or uncoordinated small-bowel motor activity, or on an osmotic basis from bacterial overgrowth associated with small-bowel stasis. Impaired glandular secretory function may cause difficulty with food intake due to decreased salivation or eye irritation due to decreased lacrimation. Occasionally, temperature elevation and vasodilation can result from anhidrosis because sweating is normally important for heat dissipation (Chap. 23). Lack of sweating after a hot bath, during exercise, or on a hot day can suggest sudomotor failure.

OH (also called orthostatic or postural hypotension) is perhaps the most disabling feature of autonomic dysfunction. The prevalence of OH is relatively high, especially when OH associated with aging and diabetes mellitus is included (Table 41-4). OH can cause a variety of symptoms, including dimming or loss of vision, lightheadedness, diaphoresis, diminished hearing, pallor, and weakness. Syncope results when the drop in BP impairs cerebral perfusion. Other manifestations of impaired baroreflexes are supine hypertension, a heart rate that is fixed regardless of posture, postprandial hypotension, and an excessively high nocturnal BP. Many patients with OH have a preceding diagnosis of hypertension or have concomitant supine hypertension, reflecting the great importance of baroreflexes in maintaining postural and supine normotension. The appearance of OH in patients receiving antihypertensive treatment may indicate overtreatment or the onset of an autonomic disorder. The most common causes of OH are not neurologic in origin; these must be distinguished from the neurogenic causes (Table 41-5). Neurocardiogenic and cardiac causes of syncope are considered in Chap. 11.