<span class="center-menu">← <small>PREVIOUS: [[4.1. Dysautonomia - Dysfunction of the autonomic nervous system]]</small> | <small>NEXT: [[4.3. Neuroendocrine dysregulation]]</small> →</span> -------- ##### Summary >[!Summary] >- impaired sympathetically mediated vasoconstriction[[#^1]] >- volume dysregulation[[#^1]] >- reduced stroke volume[[#^2]] >- reduced left ventricular mass[[#^2]] >- reduced peak oxygen uptake[[#^2]] >- cardiovascular autonomic dysfunction: abnormally increased sympathetic activity and circulating catecholamine excess and peripheral sympathetic denervation leading to central hypovolaemia (increased central sympathetic outflow would explain inadequate sinus tachycardia, whereas venous pooling and reduced preload leading to compensatory heart rate elevation would be due to peripheral sympathetic denervation)[[#^3]] >- abnormalities in nitric oxide activity in the skin causing acrocyanosis[[#^4]] >- 2-Adrenoreceptor polymorphisms may contribute to the hemodynamic diversity[[#^5]] >- low plasma, red cell, and total blood volumes[[#^6]] >- 28.9% of patients excreted less than 100 mEq/L of sodium in 24 hours, which was interpreted as consistent with a hypovolemic status[[#^7]] >- low levels of standing plasma renin activity and aldosterone compared with controls[[#^8]] >- some patients have a low-flow phenotype associated with inappropriately high plasma angiotensin II levels, reflecting reduced estimated angiotensin-converting enzyme 2 activity[[#^8]] -------- >_“POTS manifests with symptoms of cerebral hypoperfusion and excessive sympathoexcitation. The pathophysiology of POTS is heterogeneous and includes impaired sympathetically mediated vasoconstriction, excessive sympathetic drive, volume dysregulation, and deconditioning.”_ <small>([[Benarroch-2012]], [p. 1](zotero://open-pdf/library/items/WEZLT9QC?page=1&annotation=PMG9XN7R))</small>^1 >_“Most patients with POTS exhibit greater and more persistent tachycardia, reduced stroke volume, reduced left ventricular mass, and reduced peak oxygen uptake when upright and during and after exercise compared with control subjects.”_ <small>([[Benarroch-2012]], [p. 4](zotero://open-pdf/library/items/WEZLT9QC?page=4&annotation=SFDAFPMS))</small>^2 >*“Other proposed pathomechanisms include disorders of autonomic cardiovascular regulation, both abnormally increased sympathetic activity and circulating catecholamine excess [7, 50] and peripheral sympathetic denervation leading to central hypovolaemia [51–53]. According to this hypothesis, increased central sympathetic outflow would explain inadequate sinus tachycardia, whereas venous pooling and reduced preload leading to compensatory heart rate elevation would be due to peripheral sympathetic denervation (Fig. 1). Both pathomechanisms, although apparently contradictory, if acting together, would result in characteristic postural tachycardia. It is unclear whether this cardiovascular autonomic dysfunction is of hereditary or rather acquired nature” *<small>([[Fedorowski-2019]], [p. 6](zotero://open-pdf/library/items/BZ35QDLR?page=6&annotation=ICHLQE3I))</small>^3 >*“A striking physical feature in ∼50% of patients with POTS is a dependant acrocyanosis (Figure 2). These patients experience a dark red-blue discoloration of their legs (feet to above knees), which are cold to the touch. The reasons underlying this phenomenon are not clear, but may relate to abnormalities in nitric oxide activity in the skin of POTS patients” *<small>([[Raj-2013]], [p. 2](zotero://open-pdf/library/items/CCJLQKRB?page=2&annotation=CS3ECMS7))</small>^4 ##### Hemodynamic diversity in POTS >_“2-Adrenoreceptor polymorphisms may contribute to the hemodynamic diversity of patients with POTS.”_ <small>([[Benarroch-2012]], [p. 2](zotero://open-pdf/library/items/WEZLT9QC?page=2&annotation=XAZFT4SX))</small>^5 ##### Volume dysregulation in POTS >_“Many patients with POTS have low plasma, red cell, and total blood volumes as assessed using various techniques.”_ <small>([[Benarroch-2012]], [p. 3](zotero://open-pdf/library/items/WEZLT9QC?page=3&annotation=HQ2FFQIK))</small>^6 >_“In one study, 28.9% of patients excreted less than 100 mEq/L of sodium in 24 hours, which was interpreted as consistent with a hypovolemic status.”_ <small>([[Benarroch-2012]], [p. 3](zotero://open-pdf/library/items/WEZLT9QC?page=3&annotation=HUFCAVLJ))</small>^7 >_“In many cases, these patients have low levels of standing plasma renin activity and aldosterone compared with controls. However, some patients have a low-flow phenotype associated with inappropriately high plasma angiotensin II levels, reflecting reduced estimated angiotensin-converting enzyme 2 activity.”_ <small>([[Benarroch-2012]], [p. 3](zotero://open-pdf/library/items/WEZLT9QC?page=3&annotation=X5KRRGTX))</small>^8