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Table 26-1 Clinical tests of autonomic function
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Noninvasive bedside tests Blood-pressure response to standing or vertical tilt Heart rate response to standing Isometric exercise Heart rate variation with respiration Valsalva ratio (see text) Sweat tests Axon re ex Plasma noradrenaline level Plasma vasopressin level Fall in BP 30/15 mmHg Afferent and sympathetic efferent limbs Vagal afferent and efferent limbs Sympathetic efferent limb Vagal afferent and efferent limbs Afferent and efferent limbs Sympathetic efferent limb Postganglionic sympathetic efferent bers Sympathetic efferent limb Afferent limb
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Increase 11 90 beats/min; 30:15 ratio 104 Increase in diastolic BP, 15 mmHg Maximum-minimum heart rate 15 beats/min; E:I ratio 12a 14a Sweating over all body and limbs Local piloerection, sweating Rises on tilting from horizontal to vertical Rise with induced hypotension Invasive tests
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Valsalva maneuver (BP response with indwelling arterial catheter or continuous noninvasive BP measurement) Barore ex sensitivity
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Infusion of pressor drugs
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Phase I: Rise in BP Phase II: Gradual reduction of BP to plateau; tachycardia Phase III: Fall in BP Phase IV: Overshoot of BP, bradycardiaa (1) Slowing of heart rate with induced rise of BPa (2) Steady-state responses to induced rise and fall of BP (1) Rise in BP (2) Slowing of heart rate Other tests of vasomotor control
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Afferent and sympathetic efferent limbs
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(1) Parasympathetic afferent and efferent limbs (2) Afferent and efferent limbs (1) Adrenergic receptors (2) Afferent and efferent parasympathetic limbs
Radiant heating of trunk Immersion of hand in hot water Cold pressor test Emotional stress
Increased hand blood ow Increased blood ow of opposite hand Reduced blood ow, rise in BP Increased BP Tests of pupillary innervation
Sympathetic efferent limb Sympathetic efferent limb Sympathetic efferent limb Sympathetic efferent limb
4% cocaine 01% adrenaline 1% hydroxyamphetamine hydrobromide 25% methacholine 0125% pilocarpine
Pupil dilates No response Pupil dilates No response
Sympathetic innervation Postganglionic sympathetic innervation Postganglionic sympathetic innervation Parasympathetic innervation
Age-dependent response
BP, blood pressure; E:I, expiration: inspiration
Reproduced by permission from McLeod and Tuck
ralysis results in vasodilatation of skin vessels and a rise in skin temperature; vasoconstriction lowers the temperature With a skin thermometer, one may compare affected and normal areas under standard conditions The normal skin temperature is 31 to 33 C when the room temperature is 26 to 27 C Vasoconstrictor tone may also be tested by measuring the reduction in skin temperature at a distant site before and after immersing one or both hands in cold water (see the discussion of the cold pressor test, below) The integrity of the sympathetic re ex arc which includes baroreceptors in the aorta and carotid sinus, their afferent pathways, the vasomotor centers, and the sympathetic and parasympathetic out ow can be tested in a general way by combining the cold pressor test, grip test, mental arithmetic test, and Valsalva maneuver, as described below
Vasoconstriction induces an elevation of the blood pressure This is the basis of the cold pressor test In normal persons, immersing one hand in ice water for 1 to 5 min raises the systolic pressure by 15 to 20 mmHg and the diastolic pressure by 10 to 15 mmHg Similarly, the sustained isometric contraction of a group of muscles (eg, those of the forearm in handgrip) for 5 min normally increases the heart rate and the systolic and diastolic pressures by at least 15 mmHg The response in both of these tests is reduced or absent with lesions of the sympathetic re ex arc, particularly of the efferent limb, but neither of these tests has been well quantitated or validated The stress involved in doing mental arithmetic in noisy and distracting surroundings will also stimulate a mild but measurable increase in pulse rate and blood pressure Obviously this response does not depend on the afferent limb of
the sympathetic re ex arc and must be mediated by corticalhypothalamic mechanisms If the response to the Valsalva maneuver is abnormal and the response to the cold pressor test is normal, the lesion is probably in the baroreceptors or their afferent nerves; such a defect has been found in diabetic and tabetic patients and is common in many neuropathies A failure of the pulse rate and blood pressure to rise during mental arithmetic coupled with an abnormal Valsalva maneuver suggests a defect in the central or peripheral efferent sympathetic pathways Tests of Sudomotor Function The integrity of sympathetic efferent pathways can be assessed further by tests of sudomotor activity There are several of these, all somewhat cumbersome and used mainly in specialized autonomic testing laboratories; furthermore, most of them cannot differentiate central from peripheral causes of anhidrosis The simplest tests involve weighing sweat after it is absorbed by small squares of lter paper Also, powdered charcoal dusted on the skin will cling to moist areas and not to dry ones In the sympathetic or galvanic skin-resistance test, a set of electrodes placed on the skin measures the resistance to the passage of a weak current through the skin; in all likelihood, the change in electrical potential is the result of an ionic current within the sweat glands, not simply an increase in sweating that lowers skin resistance This method can be used to outline an area of reduced sweating due to a peripheral nerve lesion, since the response depends on sympathetic activation of sweat glands (Gutrecht) The starchiodine test or use of a color indicator such as quinizarin (gray when dry, purple when wet) and the more recently introduced plastic or silicone method are other acceptable procedures A more quantitative and reproducible examination of postganglionic sudomotor function, termed QSART, has been developed and studied extensively by Low It is essentially a test of distal sympathetic axonal integrity utilizing the local axon re ex A 10% solution of acetylcholine is iontophoresed onto the skin using 2 mA for 5 min Sweat output is recorded in the adjacent skin by sophisticated circular cells that detect the sweat water The forearm, proximal leg, distal leg, and foot have been chosen as standardized recording sites By this test, Low has been able to de ne patterns of absent or delayed sweating that signify postganglionic sympathetic failure in small- ber neuropathies and excessive sweating or reduced latency in response, as is seen in re ex sympathetic dystrophy This is the preferred method of studying sweating and the function of distal sympathetic bers, but its technical complexity makes it available only in specially equipped laboratories Lacrimal Function Tearing can be estimated roughly by inserting one end of a 5-mm-wide and 25-mm-long strip of thin lter paper into the lower conjunctival sac while the other end hangs over the edge of the lower lid (the Schirmer test) The tears wet the strip of lter paper, producing a moisture front After 5 min, the moistened area extends for a length of approximately 15 mm in normal persons An extent of less than 10 mm is suggestive of hypolacrimia This test is used mainly to detect the dry eyes (keratoconjunctivitis sicca) of the Sjogren syndrome, but it may also be helpful in fully studying various autonomic neuropathies Tests of Bladder, Gastrointestinal, and Penile Erectile Function Bladder function is best assessed by the cystometrogram, which measures intravesicular pressure as a function of the volume of
saline solution permitted to ow by gravity into the bladder The rise of pressure as 500 mL of uid is allowed to ow gradually into the bladder, the emptying contractions of the detrusor, and the volume at which the patient reports a sensation of bladder fullness can be recorded by a manometer (A detailed account of cystometric techniques can be found in the monograph of Krane and Siroky) A simple way of determining bladder atony (prostatic obstruction and overdistention having been excluded) is to measure the residual urine (by catheterization of the bladder) immediately after voluntary voiding or to estimate its volume by intravenous myelography or ultrasound imaging Disorders of gastrointestinal motility are readily demonstrated radiologically In dysautonomic states, a barium swallow may disclose a number of abnormalities, including atonic dilatation of the esophagus, gastric atony and distention, delayed gastric emptying time, and a characteristic small bowel pattern consisting of an increase in frequency and amplitude of peristaltic waves and rapid intestinal transit A barium enema may demonstrate colonic distention and a decrease in propulsive activity Sophisticated manometric techniques are now available for the measurement of gastrointestinal motility, especially in the esophagus (see Low et al) Nocturnal penile tumescence is recorded in many sleep laboratories and may be used as an ancillary test of sacral autonomic (parasympathetic) innervation Pharmacologic Tests of Autonomic Function The topical application of pharmacologic agents is particularly useful in evaluating pupillary denervation Part of the rationale behind these special tests is Cannon s law, or the phenomenon of denervation hypersensitivity, in which an effector organ, 2 to 3 weeks after denervation, becomes hypersensitive to its particular neurotransmitter substance and related drugs The instillation of a 1:1000 solution of epinephrine into the conjunctival sac has no effect on the normal pupil but will cause the sympathetically denervated pupil to dilate (3 drops instilled three times at 1-min intervals) The pupillary size is checked after 15, 30, and 45 min As a rule, hypersensitivity to epinephrine is greater with lesions of postganglionic bers than of preganglionic bers If denervation is incomplete, the hypersensitivity phenomenon may not be demonstrable Also, in lesions that involve central sympathetic pathways, the pupil rarely reacts to this test More reliable as a test of sympathetic denervation is the topical application into the conjunctival sac of a 4 to 10% cocaine solution that potentiates the effects of NE by preventing its uptake The test should be carried out as described above A normal response to cocaine consists of pupillary dilatation In sympathetic denervation caused by lesions of the post- or preganglionic bers, no change in pupillary size occurs, since no transmitter substance is available The reason for lack of response in chronic preganglionic lesions is presumed to be a depletion of NE in the postganglionic bers In cases of central sympathetic lesions, slight mydriasis occurs These and other pharmacologic methods of evaluating pupillary disturbances are considered more fully in Chap 14 and are outlined in Fig 14-8 Cutaneous Flare Response The intracutaneous injection of 005 mL of 1:1000 histamine phosphate normally causes a 1-cm wheal after 5 to 10 min This is surrounded by a narrow red areola, and it, in turn, by an erythematous are that extends 1 to 3 cm beyond the border of the wheal A similar triple response follows the
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