Blair P. Grubb and Beverly Karabin

Chapter Outline

Autonomic Nervous System

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

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

In a healthy individual, close to 25% to 30% of the body’s blood volume is in the thorax while supine.² 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 volume drop of 25% to 30% occurs in the first few moments of standing, resulting in a decline in venous return to the heart. As a result, the heart can pump only the blood that it receives, which produces a decline in stroke volume of approximately 40% and a decline in arterial blood pressure. The area around which these changes occur is known as the venous hydrostatic indifference point (HIP), and it represents the point in the vascular system where it 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 use of 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 approximately 30 minutes of upright posture and can result in a decline in plasma volume of close to 10%.

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 Lieshout² have described three phases of orthostatic response: (1) the initial response (in the first 30 seconds), (2) the early steady state alteration (at 1 to 2 minutes), and (3) the prolonged orthostatic period (after at least 5 minutes upright).

In the first moments following head-up tilt, cardiac stroke volume remains constant despite the decline in venous rhythm, 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 in 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 are mechanoreceptors connected by vagal afferents in each of the four cardiac chambers. These mechanoreceptors affect a tonic inhibitory effect on the cardiovascular regulatory centers of the medulla (especially the nucleus tractus solitarii). The baroreceptor neurons located here can directly activate the cardiovagal neurons of the nucleus ambiguous and dorsal vagal nucleus, while simultaneously inhibiting 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 the firing rates decrease, there is a change in the systemic resistance vessels and the splanchnic capacitance vessels. In addition, there is a focal axon reflect (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. The mechanoreceptors are located here 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 the 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 leg 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 causes an activation of the low-pressure receptors of the heart. This action 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 change can allow a fall in mean arterial pressure of up to 20 mm Hg that can last for 6 to 8 seconds. The same mechanisms used during head-up tilt then compensate for this decline in pressure.

The early steady state adjustments to upright posture consist of an increase in heart rate of approximately 10 to 15 beats/min, an increase 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 a given moment, approximately 5% of the body’s blood is in the capillaries, 8% is in the heart, 12% is in the pulmonary vasculature, 15% is in the arterial system, and 60% is in the venous system. The inability of any one of these mechanisms to operate adequately (or in a coordinated manner) can result in a failure of the body to compensate for an initial or prolonged orthostatic challenge. This, in turn, would result in systemic hypotension that, if sufficiently profound, could lead to cerebral hypoperfusion and subsequent loss of consciousness.

Historical Perspective

By the middle of the nineteenth century, physicians began to report on a group of patients who had developed a disorder characterized by exercise intolerance, severe fatigue, and palpitations.³ 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 called “irritable heart syndrome”.⁴

Around the time of the World War I, a condition referred to as neurocirculatory asthenia began to be reported. The most remarkable of these was a study by Thomas Lewis, who described a condition he called the “effort syndrome.”⁵ He stated that the 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 (bpm) supine to 120 bpm while upright. In some of these patients, there was a significant decline in blood pressure while upright, whereas others demonstrated only a modest decline.⁶ 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,” oftentimes accompanied by a compensatory tachycardia. Lewis further wrote that the reduction in blood flow “may be sufficient to produce cerebral anemia.”

Additional reports appeared,7,8 and this condition was later elucidated by Schondorf and Low, who performed extensive evaluations of 16 patients who suffered from extreme fatigue, exercise intolerance, bowel hypomotility, and lightheadness.⁹ 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 bpm within the first 2 to 5 minutes of upright tilt. Some of these patients became hypotensive, but the majority remained normotensive, and a small percentage became hypertensive. In describing the condition, they used the term “postural orthostatic tachycardia syndrome” (POTS).¹⁰ Later investigations have found that POTS is not a single entity; rather, it is a heterogeneous group of disorders with similar clinical characteristics.^6,11,12

Definitions

The hallmark of these disorders is orthostatic intolerance, the definition of which is the occurrence of symptoms upon standing that 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 can 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 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 the symptoms can 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 104-1.