functional hyperemia in response to cognitive challenge under orthostatic stress – perhaps related to a loss of autoregulatory buffering of beat-by-beat fluctuations in arterial blood flow. Causes The symptoms of POTS can be caused by several distinct pathophysiological mechanisms. These mechanisms are poorly understood, and can overlap, with many patients showing features of multiple POTS types. Many people with POTS exhibit low blood volume (hypovolemia), which can decrease the rate of blood flow to the heart. To compensate for low blood volume, the heart increases its cardiac output by beating faster, leading to the symptoms of presyncope and reflex tachycardia. In the 30% to 60% of cases classified as hyperadrenergic POTS, norepinephrine levels are elevated on standing, often due to hypovolemia or partial autonomic neuropathy. A smaller minority of people with POTS have (typically very high) standing norepinephrine levels that are elevated even in the absence of hypovolemia and autonomic neuropathy; this is classified as central hyperadrenergic POTS. The high norepinephrine levels contribute to symptoms of tachycardia. Another subtype, neuropathic POTS, is associated with denervation of sympathetic nerves in the lower limbs. In this subtype, it is thought that impaired constriction of the blood vessels causes blood to pool in the veins of the lower limbs. Heart rate increases to compensate for this blood pooling. In up to 50% of cases, there was an onset of symptoms following a viral illness. It may also be linked to vaccination, physical trauma, concussion, pregnancy, or surgery. It is believed that these events could act as a trigger for an autoimmune response that result in POTS. Covid has been implicated as has more rarely, the vaccine for COVID. It has been shown to emerge in previously healthy patients after COVID-19, or in rare cases after COVID-19 vaccination. POTS is more common in females than males. It has also been shown to be linked in patients with acute stressors such as pregnancy, recent surgery, or recent trauma. POTS also has been linked to patients with a history of autoimmune diseases, Long Covid, irritable bowel syndrome, anemia, hyperthyroidism, fibromyalgia, diabetes, amyloidosis, sarcoidosis, systemic lupus erythematosus, and cancer. Genetics likely plays a role, with one study finding that one in eight POTS patients reported a history of orthostatic intolerance in their family. Autoimmunity There is an increasing number of studies indicating that POTS is an autoimmune disease. A high number of patients has elevated levels of