Why do patients have orthostatic symptoms in POTS

On the patient's going from lying to standing up, there is a momentary fall in pulse pressure, sensed by baroreceptors, whose unloading results in an autonomically mediated increase in heart rate (HR) and in systemic vascular resistance that restores the cardiovascular status quo. Patients with generalized autonomic failure (pure autonomic failure, multiple system atrophy, autonomic neuropathies) have orthostatic hypotension with symptoms of light-headedness, weakness, blurred vision, and impaired cognition [1]. These symptoms are most likely a result of cerebral hypoperfusion. When autonomic failure is incomplete, compensatory autonomic overreaction occurs, resulting in symptoms such as palpitations, tremulousness, vasomotor symptoms (eg, coldness, acrocyanosis), and nausea. Thus almost paradoxically, patients with partial dysautonomia may be more clinically symptomatic than those with more complete autonomic dysfunction. Patients with the postural tachycardia syndrome (POTS) [2] are characterized by excessive orthostatic tachycardia without hypotension associated with lightheadedness, palpitations, tremulousness, and nausea. Other symptoms that occur while in the upright position and which resolve themselves while supine include tunnel vision, weakness, fatigue, difficulty breathing, and pains (chest, acral). The intensity and frequency of symptoms is often variable and in some instances may occur even when the patient is supine. We believe that we understand some of the symptoms of POTS although our understanding is far from complete. For example, during upright posture, some patients increase depth of respiration, causing hypocapnia and cerebral vasoconstriction [3], thereby causing symptoms of lightheadedness, visual blurring (tunneling), and weakness. However, these symptoms can develop in the absence of hypocapnia and decreased cerebral perfusion. Sympathetic overaction, well documented by observations such as increased orthostatic plasma norepinephrine [4] and sympathovagal index [5], result in palpitations, tremulousness, nausea, and weakness. The etiology of this sympathetic overactivity is multifactorial and in many cases is poorly defined. There are other symptoms whose pathophysiology is unexplained. These include chest and limb pain, head pain, difficulty breathing, and episodic symptoms (autonomic storms). The mechanism of chronic fatigue is also unknown, although a relation between orthostatic intolerance and chronic fatigue has been hypothesized [6]. There are also symptoms that suggest an atypical panic disorder. These include symptoms of impending doom associated with palpitations, sweating, shaking, smothering and choking sensation, dizziness, derealization or depersonalization, and finally, fear of losing control or dying. In reality, there are many instances where the interplay of physiologic and psychologic mechanisms is difficult or impossible to differentiate. The clinical dilemma is confounded by the rejection by many patients of any psychosomatic mechanisms. We find a pragmatic integrated model of episodic and orthostatic dysautonomia to be helpful. This model recognizes final autonomic effector pathways with multiple peripheral and central inputs. We have found that some of these patients have a restricted form of sympathetic autonomic neuropathy that spares parasympathetic cardiovagal function [2]. This observation is important and may unify many of the disparate observations made in POTS. A selective autonomic neuropathy that predominantly affected the lower extremities may explain the excessive venous pooling seen in POTS [2,7,8]. A selective impairment of renal sympathetic innervation may explain the decreases in plasma volume or red cell mass found in some patients [9]. Denervation supersensitivity may explain the cardiac 13-adrenergic hypersensitivity seen in POTS [10]. Alternatively, this excessive HR response may be a result of reduced vagal cardioinhibitory activity (vagal braking effect) or of a compensatoty HR response to enhanced [3-adrenergic vasodilatation. The exaggerated venous pooling of patients with POTS may be the result of a primary impairment of arterial