Orthostatic intolerance...

Orthostatic intolerance is an umbrella term for several conditions in which symptoms are made worse by upright posture. This document has been prepared for those who have requested further information about neurally mediated hypotension (NMH) and postural tachycardia syndrome (POTS), two common forms of chronic orthostatic intolerance. Hypotension is the medical term for low blood pressure (BP), and tachycardia is the medical term for an increased heart rate (HR).

What are NMH and POTS?

Neurally mediated hypotension refers to a drop in blood pressure that occurs after being upright. We define NMH by a drop in systolic BP of 25 mm Hg (compared to the BP measured when the person is lying flat) during standing or upright tilt table testing. Although NMH may be slightly more common in people with a low resting blood pressure, most people who develop NMH during standing have a normal resting blood pressure. NMH is an abnormality in the regulation of blood pressure during upright posture. It occurs when too little blood circulates back to the heart when people are upright, and triggers an abnormal reflex interaction between the heart and the brain. NMH is sometimes known by the following names: the fainting reflex, delayed orthostatic hypotension, neurocardiogenic syncope, vasodepressor syncope, vaso-vagal syncope. Syncope is the medical term for fainting.

Postural tachycardia syndrome refers to an exaggerated increase in heart rate with standing. A healthy individual usually has a slight increase in heart rate-by about 10-15 beats per minute--within the first 10 minutes of standing. POTS is considered present if the heart rate increases by 30 beats per minute, or if it reaches 120 beats per minute or higher over the first 10 minutes of standing. POTS is an abnormality in the regulation of heart rate, not necessarily in the resting heart itself. Some patients with POTS in the first 10 minutes of upright standing or tilt testing will go on to develop NMH if the test is continued; the two conditions often are found together, and they are not mutually exclusive diagnoses.

How does upright posture lead to these problems?

When a healthy individual stands up, gravity causes about 10-15% of his or her blood to settle in the abdomen or limbs. This pooling of blood means that less blood reaches the brain, the result of which can be a feeling of lightheadedness, seeing stars, darkening of vision, or even fainting. For most of us, this lightheaded feeling is infrequent when we stand up because the body turns on a series of rapid reflex responses. To make up for the lower amount of blood returning to the heart immediately after standing, the body releases norepinephrine and epinephrine (also known as adrenaline). These substances typically cause the heart to beat a little faster and with more force (a familiar feeling after we exercise or are frightened), and cause the blood vessels to tighten or constrict. The end result is more blood returning to the heart and brain. Most of the time, we are unaware of these reflex changes in blood flow when we stand up.

When people with either NMH or POTS are upright, they appear to pool a larger amount of blood in vessels below the heart. More blood settles in the limbs the longer the person remains upright. The body responds by releasing more norepinephrine or epinephrine, in an attempt to cause more constriction of the blood vessels. For a variety of reasons, not all of which are well understood, the blood vessels do not seem to respond normally to these substances (either they dilate too much or they do not constrict efficiently). Because the heart remains able to respond, we often see an increased heart rate.

In those with POTS, the main result of excessive pooling of blood during upright posture is an exaggerated rise in heart rate. In those with NMH, the main result is a reflex lowering of blood pressure. Some of this is caused by a "miscommunication" between the heart and the brain, both of which usually are structurally normal. Just when the heart needs to beat faster to pump blood to the brain and prevent fainting, the brain sends out the message that the heart rate should be slowed down, and the blood vessels should dilate further. These actions take even more blood away from the central part of the circulation where it is needed. At this time, it is not entirely clear why some people develop NMH and some develop POTS, although it may relate in part to the balance of epinephrine and norepinephrine release in the system.

Which symptoms can be caused by NMH or POTS?

Any time the brain is getting too little blood flow, the usual result is a lightheaded or spacey feeling. Recurrent lightheadedness is a common symptom of both NMH and POTS. If lightheadedness is severe, individuals may have dimming of their vision, may hear sounds as though they were far away, and may have nausea or vomiting. They may faint because not enough blood is getting to the brain. Fainting is helpful, in that it restores a person to the flat position, removing the effect of gravity on blood pooling in the limbs, and allowing more blood to return to the heart. Following the episodes of lightheadedness or fainting, most people feel tired for several hours (sometimes more than a day) and their thinking can be somewhat foggy. Some patients with NMH experience prolonged fatigue after a modest amount of physical activity, or after sustaining quiet activity like sitting at a desk. This fatigue after exertion or sustained activity can also last 24-72 hours, and can interfere with many daily activities.

While fainting has been considered a classic symptom of NMH, we have found that many persons who develop NMH during tilt table testing do not faint in day-to-day life. Chronic fatigue, muscle aches (or myalgias), headaches, and mental confusion can be prominent symptoms of NMH in these individuals. The mental confusion takes the form of difficulty concentrating, staying on task, paying attention, remembering, or finding the right words. Some describe being in a "mental fog." Some develop worse fatigue after mentally demanding activities, such as reading and concentrating. This may occur because the blood vessels of the limbs dilate rather than constrict in response to mental tasks, allowing more blood to pool.

In persons with POTS, a fast heart rate is a defining feature, and awareness of vigorous or skipped heart beats (palpitations) is common. In addition, patients can experience lightheadedness, intolerance of exercise, fatigue, visual blurring, weakness, imbalance, headaches, shakiness, clamminess, anxiety, shortness of breath, and the same type of mental fogginess that those with NMH describe.

It has now been established that there is a substantial overlap between syndromes of orthostatic intolerance on the one hand, and either chronic fatigue syndrome (CFS) or fibromyalgia (FM) on the other. It needs to be emphasized that not all those with NMH or POTS have CFS or FM, and not all with CFS or FM have NMH or POTS.

When do NMH and POTS lead to symptoms?

Symptoms of NMH and POTS usually are triggered in the following settings:

with quiet upright posture (such as standing in line, standing in a shower, or even sitting at a desk for long periods),

after being in a warm environment (such as in hot summer weather, a hot crowded room, a hot shower or bath),
immediately after exercise,
after emotionally stressful events (seeing blood or gory scenes, being scared or anxious).

in some people, after eating, when blood flow shifts to the intestines during digestion.

if fluid and salt intake are inadequate
It is thought that we all would develop NMH provided that the environmental conditions were sufficiently severe: for example, if we did not take in enough fluids or salt, or were subjected to extremely prolonged periods of upright posture or to very warm environments. The reflex response that results in lowered blood pressure simply occurs at an earlier point in some individuals. Each person's susceptibility is affected by a number of factors, including genetics, diet, psychological make-up, and the presence of other medical disorders including infection, inflammation, or allergy. Some people may develop NMH or POTS during tilt testing, but not be affected much in regular daily life. A person is treated for NMH or POTS when there is enough early triggering of symptoms to interfere with normal activity.

How are NMH and POTS diagnosed?

NMH and POTS cannot be detected with routine, resting blood pressure or heart rate screening. The diagnoses can be made with a prolonged standing test or a tilt table test. Although a 10-minute test is all that is needed to diagnose POTS, this is too brief for diagnosing NMH, which usually requires at least a 45-minute period of upright posture. Many hospitals and academic centers throughout the world perform tilt table testing. It allows careful measurement of the heart rate and blood pressure responses to the head-up position, usually at a 70-degree angle, in an almost standing position. The usual reason for performing a tilt table test in the past had been for the evaluation of recurrent fainting. Many people with NMH develop adaptations to keep from fainting, such as crossing their legs, fidgeting, or sitting or lying down when they get lightheaded or tired. However, during the tilt table test they must remain still, and they cannot call upon these natural defenses. As a result, fainting can occur for the first time during the tilt table test. Increased fatigue and malaise often occur for a few days after the test is performed.

What causes NMH or POTS?

The answer to this question isn't well understood at present. We suspect NMH and POTS have genetic origins in many people, because it is not uncommon for us to find several affected individuals with some form of orthostatic intolerance in the same family. No gene for NMH has been identified, but one rare genetic cause has been found for POTS. One trait seen with increased frequency in those with CFS and orthostatic intolerance is excessive joint mobility, for reasons that are not yet clear. A number of persons with NMH or POTS report that their symptoms began after an infection or physical trauma (such as a flu, mononucleosis, a car accident, or surgery). Other environmental factors may also play a role, but more research is needed before we will know what actually causes either condition. Some investigators have noted an overlap in the symptoms of fatigue and conditions in which there is too little room for the spinal cord in the neck or as it emerges from the skull (conditions known as cervical spine stenosis or Chiari malformation). It needs to be emphasized that these conditions do not explain the presence of POTS or NMH in the vast majority of patients, and further studies are needed regarding the best methods to diagnose and treat these abnormalities.

One of the most common and treatable problems identified in those with NMH and POTS is a low salt (sodium) intake in the diet. Salt helps us retain fluid in the blood vessels, and helps maintain a healthy blood pressure. Salt has received bad press in the last couple of decades because a high salt diet in some individuals with high or high-normal blood pressure can lead to further increases in blood pressure, and thereby to heart disease and stroke. This has led to general health recommendations to "cut down on salt." As we are finding, this general recommendation isn't right for all people.

In adults, an average blood pressure is 120/70. An adult's systolic blood pressure [the top number] is considered low if it is below 100, and it is considered elevated if it is above 140. An adult's diastolic blood pressure [the bottom number] is considered high if it is over 90. Normal values for BP in children and adolescents vary by age and weight. Individuals can have NMH at a wide range of resting blood pressures. It may be slightly more common in those whose systolic BP is in the 90-110 range. For individuals with NMH, a low salt intake may be unhealthy, and reducing sodium intake may move them from feeling good to developing the symptoms of fatigue and lightheadedness described earlier. In experimental work earlier this century, severe short-term salt depletion led to fatigue and mental dulling in the adult research participants.