Postural Orthostatic Tachycardia Syndrome

Autonomic Nervous System

To survive in the world, all organisms must possess the ability to make rapid alterations that stably maintain their internal environments despite significant changes in their external environments. This encompasses not only changes in environmental temperature, barometric pressure, and humidity but also the capability to quickly respond to sources of possible danger. The major natural processes through which this “homeostasis” is sustained and regulated are controlled by the hypothalamus and its effects on two systems: the ANS and the endocrine system.

Although the assumption of upright posture was one of the truly defining moments in the process of human evolution, it had the effect of placing the organ that most defines our humanity, the brain, in a somewhat precarious position in regard to the maintenance of constant oxygenation because the blood pressure–regulating system had evolved principally to meet the needs of an animal in a dorsal position. The ANS is the principal modality for both short- and long-term changes in position. Although the renin-angiotensin-aldosterone system also plays a role, it does so over a much longer period of time.

In a normal individual, close to 25% to 30% of the body’s blood volume is in the thorax when supine. Upon standing, the effect of gravity is to displace approximately 300 to 800 mL of blood downward to the abdomen and lower extremities. This is a volume drop of roughly 25% to 30% in the thorax, and it occurs in the first few moments of standing, resulting in a decline in the venous return to the heart. Because the heart can only pump the blood that it receives, this produces an approximately 40% decline in the stroke volume and a decline in the arterial blood pressure. The area around which these changes occur is referred to as the venous hydrostatic indifference point (HIP) and represents the point in the vascular system where blood pressure is independent of position. The arterial HIP is near the level of the left ventricle, and the venous HIP is around the diaphragm.

Standing also results in a substantial rise in the transmural capillary pressure that is present in the dependent areas of the body, resulting in a rise in fluid filtration into the tissue spaces. This process arrives at a steady state after around 30 minutes of upright posture and can result in close to 10% decline in the plasma volume.

Adequate maintenance of cerebral perfusion during upright posture is the product of the interaction of several cardiovascular regulatory systems. The exact changes that occur with standing (an active process) differ somewhat from those seen during head-up tilt (a more passive process). Wieling and van Lieshout have described three phases of orthostatic response: (1) the initial response (in the first 30 seconds), (2) the early steady-state alteration (at 1–2 minutes), and finally (3) the prolonged orthostatic period (after at least 5 minutes upright).

In the first moments after head-up tilt, cardiac stroke volume remains constant despite the decline in venous return (possibly because of the blood in the pulmonary circulation). Afterward, there is a gradual fall in both cardiac filling and arterial pressure. This results in actuation of two distinct sets of pressure receptors compressed by high-pressure receptors in the carotid sinus and aortic arch, as well as low-pressure receptors in the heart and lungs. In the heart, mechanoreceptors connected by vagal afferents in each of the four cardiac chambers are present. These mechanoreceptors have a tonic inhibitory effect on the cardiovascular regulatory centers of the medulla (especially the nucleus tractus solitarii). The baroreceptive neurons located here can directly activate the cardiovagal neurons of the nucleus ambiguous and dorsal vagal nucleus and, at the same time, inhibit the sympathoexcitatory neurons of the rostral ventrolateral medulla.

The reduced venous return and fall in filling pressure that occur during upright posture reduce the stretch on these receptors. As their firing rates decrease, there is a change in not only the systemic resistance vessels but also the splanchnic capacitance vessels. In addition, there is a local axon reflex (the venoarteriolar axon reflex) that can constrict flow to the skin, muscle, and adipose tissue. This may contribute up to 50% of the increase in limb vascular resistance seen during upright posture.

During head-up tilt, there is also activation of the high-pressure receptors in the carotid sinus. The carotid sinus contains a group of baroreceptors and nerve endings located in the enlarged area of the internal carotid artery, just after its origin from the common carotid artery. Here, the mechanoreceptors are located in the adventitia of the arterial wall. The afferent impulses generated by stretch on the arterial wall are then transmitted via the sensory fibers of the carotid sinus nerve that travels with the glossopharyngeal nerve. These afferent pathways terminate in the nucleus tractus solitarii in the medulla, near the dorsal and ambiguous nuclei. The initial increase in heart rate seen during tilt is thought to be modulated by a decline in carotid artery pressure. The slow rise in diastolic pressure seen during upright tilt is believed to be more closely related to a progressive increase in peripheral vascular resistance.

The circulatory changes seen during standing are somewhat different from those seen during tilt. Standing is a much more active process that is accompanied by contractions of muscles of both the legs and abdomen, which produces a compression of both capacitance and resistance vessels and results in an elevation in peripheral vascular resistance. This increase is sufficient to cause a transient increase in both right atrial pressure and cardiac output, which, in turn, cause an activation of the low-pressure receptors of the heart. This provokes an increase in neural traffic to the brain, with a subsequent decrease in peripheral vascular resistance, which can fall as much as 40%. This can allow a fall in mean arterial pressure of up to 20 mm Hg that can last for up to 6 to 8 seconds. The decline in pressure is then compensated for by the same mechanisms as during head-up tilt.

The early steady-state adjustments to upright posture consist of an increase in the heart rate of approximately 10 to 15 beats/min, an increase in diastolic blood pressure of approximately 10 mm Hg, and little or no change in systolic blood pressure. At this point, compared with supine posture, the blood volume of the thorax has fallen by 30%, cardiac output has increased by 30%, and heart rate is 10 to 15 beats/min higher.

At any given moment, approximately 5% of the body’s blood is in the capillaries, 8% in the heart, 12% in the pulmonary vasculature, 15% in the arterial system, and 60% in the venous system. The inability of any one of these mechanisms to operate adequately (or in a coordinated manner) may result in a failure of the body to compensate for either an initial or prolonged orthostatic challenge. This, in turn, would result in systemic hypotension, which, if sufficiently profound, could lead to cerebral hypoperfusion and subsequent loss of consciousness.

Historical Perspective

By the middle of the 19th century, physicians had begun to report on a group of patients who had developed a disorder characterized by exercise intolerance, severe fatigue, and palpitations. These symptoms would often appear suddenly without a discernible cause (such as prolonged immobility, blood loss, or dehydration). At the time of the American Civil War, DeCosta described patients suffering from postural tachycardia and orthostatic intolerance, a condition he referred to as “irritable heart syndrome.”

Around the time of World War I, a condition referred to as “neurocirculatory asthenia” began to be reported. The most remarkable of such reports was a study by Thomas Lewis, who described a condition he referred to as “the effort syndrome.” In the paper, he stated that fatigue was “an almost universal complaint” among these patients, as well as exercise intolerance in conjunction with symptoms such as palpitations, chest pain, syncope, and near syncope. In addition, Lewis reported that these patients demonstrated a significant postural tachycardia, with heart rates changing from 85 beats/min when supine to 120 beats/min when upright. In some of these patients there was a significant decline in blood pressure when upright, whereas others demonstrated only a modest decline. Lewis concluded that in these patients “the potential reservoir in the veins takes up the blood, the supply to the heart falls away, and the arterial pressure falls rapidly,” often accompanied by a compensatory tachycardia. Lewis further wrote that the reduction in blood flow “may be sufficient to produce cerebral anemia.”

Over the ensuing years, additional reports appeared. ^, This condition was later expanded on by Schondorf and Low, who performed extensive evaluations in 16 patients who suffered from extreme fatigue, exercise intolerance, bowel hypomotility, and lightheadedness. During head-upright tilt-table testing, these individuals displayed distinctly abnormal cardiovascular responses to upright posture, with heart rate elevations to as high as 120 to 170 beats/min within the first 2 to 5 minutes of upright tilt. Although some of these patients became hypotensive, the majority remained normotensive (and a small percentage became hypertensive). In describing the condition, Schondorf and Low used the term postural orthostatic tachycardia syndrome (POTS).

Later investigations have found that POTS is not a single entity but rather a heterogeneous group of disorders with similar clinical characteristics.

Definitions

The hallmark of these disorders is orthostatic intolerance, the definition of which is the occurrence of symptoms upon standing, which are generally relieved by becoming supine. As noted earlier, these patients will complain of symptoms such as palpitations, fatigue, exercise intolerance, lightheadedness, nausea, headache, near syncope, and syncope. Because the amount of autonomic failure that these patients exhibit is not severe and the physical findings are often subtle, they may be misdiagnosed as having chronic anxiety or a panic disorder.

Some patients can be so severely affected that the regular activities of daily life, such as housework, bathing, and even eating, can greatly exacerbate symptoms. Studies have shown that some patients with POTS can suffer from the same degree of functional impairment as patients with congestive heart failure or chronic obstructive pulmonary disease. Interestingly, the severity of symptoms may be greater in patients with POTS than in those with more severe autonomic failure syndromes, such as pure autonomic failure. A grading system to classify the severity of orthostatic intolerance has been developed (similar to that used in congestive heart failure) as noted in Box 105.1 .