Dysautonomia. A Barely Known Disease

Dysautonomia is a disorder that occurs when an alteration happens in the functioning of the autonomic nervous system (ANS), responsible for involuntarily regulating multiple functions of the body such as heart rate, blood pressure, digestion, body temperature, and many other vital activities. Unlike voluntary movements such as walking or talking, the functions controlled by the ANS do not require our consciousness to be stable.

For example, we don’t decide when our heart should beat or how the stomach, kidneys, or glands like the pituitary and thyroid should work. This automatic regulation allows us to dedicate ourselves to thinking, moving, or performing daily activities without worrying about the internal functioning of our organs. The main function of the ANS is to maintain homeostasis, that is, the balance of the internal medium within environmental changes.

The ANS is divided into three components: the sympathetic, the parasympathetic, and the enteric. The first two are widely distributed throughout the body and usually act in a complementary way: while one stimulates certain functions, the other inhibits them. The enteric system is limited to the gastrointestinal tract and regulates its functions more independently.

Dysautonomia occurs when the ANS is unable to adequately perform its regulatory function resulting in a series of alterations that affect multiple organs and systems. Although the concept of dysautonomia began to develop clinically in the 20^th century, especially from cases of postural hypotension of neurogenic origin in the 1920s, for a long time it was a little known disease and barely recognized by doctors, not necessarily because it was rare, but because it was rarely considered as a diagnostic possibility.

Interestingly, it was in cardiology that this condition began to be studied in greater detail, since some of its most visible symptoms affect the cardiovascular system. Today, specialists in cardiology as well as neurology treat patients with dysautonomia. However, many people with this disorder go through several specialists before receiving an accurate diagnosis.

Under normal conditions, the body adapts to changes in the internal or external environment through the ANS. For example, exercising increases blood pressure, heart rate, and breathing, to ensure that muscles receive enough oxygen and glucose. When at rest, these parameters are reduced. In people with dysautonomia, the ANS is not able to generate these adequate responses, which can cause symptoms such as exercise intolerance, dizziness, or fatigue.

PRIMARY DYSAUTONOMIAS
Primary dysautonomias are those that originate from alterations of the autonomous system, either in its control centers or in its peripheral pathways. This type of dysautonomia is poorly understood, which makes it difficult to diagnose and treat. It is estimated that it affects approximately one in 10 thousand people. Although there is no cure, the treatment is symptomatic and seeks to improve the patient’s quality of life.

Because of the broad regulatory role of the ANS, its dysfunction can produce a diverse set of symptoms, complicating its identification. It is common for these symptoms to be confused with diseases of the affected organs. However, there are characteristic signs that may lead to suspicion of dysautonomia, such as chronic fatigue, dizziness, exercise intolerance, excessive sweating, dry mucous membranes, insomnia, anxiety, fluctuations in blood pressure and heart rate, nausea, blurry vision, or fainting.

To diagnose dysautonomia there are several clinical tests. Some of them measure changes in a person’s blood pressure and heart rate as they go from lying down to standing or bending over. Levels of norepinephrine (a neurotransmitter) in blood or urine may also be assessed, or the activity of autonomic nerves may be measured.

Among the most common primary dysautonomies is the orthostatic intolerance syndrome, which can present in two ways: the first is postural orthostatic tachycardia syndrome (POTS), which is characterized by an excessive increase in heart rate (more than 30 beats per minute) when standing up, without a significant drop in blood pressure. This occurs due to a collection of blood in the spleen and muscles that activates the sympathetic system causing tachycardia. The second way is orthostatic hypotension: it presents as a drop of at least 20 millimeters of mercury (mmHg) in systolic pressure and ten mmHg in diastolic pressure when standing up. In this case, the ANS fails to activate the vasoconstriction necessary to counteract the effect of gravity.

SECONDARY DYSAUTONOMIAS
Secondary dysautonomias appear as a result of other diseases such as kidney failure, some types of cancer, autoimmune diseases (e.g. Guillain-Barré syndrome), infections such as COVID-19, and metabolic conditions such as type 2 diabetes.

In recent years, there has been a debate about whether secondary dysautonomias are only consequences of other diseases or whether they could, in some cases, precede them and contribute to their appearance. To explore this hypothesis, in our laboratory we studied animal models of hypertension and metabolic syndrome. We found that some autonomic parameters were altered before these diseases develop. This suggests that certain signs of dysautonomia could serve as early or even predictive markers of the development of these diseases.

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