Upright posture is a fundamental human activity requiring rapid and effective circulatory and neurologic compensations in order to maintain blood pressure and consciousness. The orthostatic tachycardia syndrome is a disabling disease state described at least since 1940 and is the most common reason for referral for chronic orthostatic intolerance. Patients are often unable to hold jobs or attend schools. Yet, our understanding of its pathophysiology remains incomplete. An operational definition of the syndrome (often denoted by the acronym POTS for postural orthostatic tachycardia syndrome) includes symptoms of orthostatic intolerance associated with an increase in heart rate from the supine to upright position of more than 30 beats per minute or to a heart rate greater than 120 beats per minute within 10 minutes of head-up tilt (HUT). An exaggerated increase in heart rate, often accompanied by hypotension in association with dizziness, nausea, palpitations, heat and fatigue in the upright position has been described under other names including the hyperadrenergic syndrome of Streeten, idiopathic hypovolemia of Fouad et al, and most recently the postural orthostatic syndrome of Low et al. POTS is common, affecting an undisclosed number of patients mostly in the age range of 12 to 50 years, mostly female (approximately 80%), often with onset following a viral infection or other inflammatory condition. There is an as yet undetermined but increasing apparent prevalence in children and adolescents. Resting tachycardia is common. Symptoms of anxiety may proliferate and appear to be autonomically mediated in many cases; there is also overlap with anxiety/panic disorder.
Patterns of heart rate and blood pressure variation are shown in the figure and are from our paper which was the first to directly discuss POTS in the pediatric population.
POTS has been proposed as a mechanism for symptoms of the Chronic Fatigue Syndrome in a series of adult patients. POTS and CFS may share a common pathophysiology particularly in the young . Recently, a review of patients with delayed orthostatic hypotension (delayed POTS) demonstrated a high degree of association with chronic fatigue. Our preliminary data have shown that POTS physiology underlies orthostatic intolerance in the large majority of adolescents with the chronic fatigue syndrome (CFS). In those patients we demonstrated loss of heart rate variability consistent with vagal withdrawal, increased blood pressure variability consistent with enhanced modulation of sympathetic tone, and impaired baroreflex with a phase shift causing wide blood pressure swings uncompensated by compensatory HR changes. Preliminary vascular data suggest that these autonomic findings are associated with changes in arterial and venous properties of the lower limbs during orthostasis causing fluid collection in excess of ordinary "pooling" observed in control patients.
Pooling in the lower body due to gravity is believed to cause the findings. Indeed pooling changes were found in early work and may be quite striking. Maneuvers to increase effective blood volume such as acute saline loading and lower body compression with pressure suits will reverse symptoms and signs temporarily.
The literature contains a number of potential explanations for abnormal venous pooling and fluid collection in POTS including impaired innervation of the veins or in their response to sympathetic stimulation. One such explanation favors an autonomic neuropathy that predominantly affects the lower extremities. Alpha1-adrenergic denervation hypersensitivity results. A second explanation invokes decreased alpha1- receptor sensitivity; a third, beta 1-receptor supersensitivity, a fourth altered venoconstriction, while a fifth suggests increased capillary filtration as an explanation. However, alpha 1-adrenergic control of venous filling in response to baroreflex stimulation during orthostasis is important only in skin and splanchnic circulations in humans while involvement of skeletal muscle alpha 1-receptors remain controversial. Beta-adrenergic effects may also alter venous filling, but only indirectly through arterial vasoactivity and this mechanism may be most important during exogenous beta-agonist administration (isoproterenol) or during endogenous epinephrine release later during HUT. It is uncertain how important active venoconstriction is to the orthostatic response. Finally, venous capacitance properties in POTS could be abnormal because of altered vascular structure, altered muscle tone or both.
We noted a high incidence of acral findings in CFS and POTS patients during HUT. Patients had swelling of the dependent lower extremities with purplish discoloration of the dorsum of the foot and ankle. The figure shows early published data depicting percent change in mid-calf circumference from baseline prior to tilt until the end of tilt just prior to being placed supine. The data suggest a significantly greater percent increase in circumference in POTS patients compared with syncope patients or control subjects as the result of increased pooling. Clinically, there was coolness with livedo reticularis suggesting arterial malperfusion, venous dysfunction or both.