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Vanderbilt Autonomic Dysfunction Center

Pathophysiology

Patients with OI typically have:

 

  • Exaggerated increase in heart rate on standing, usually greater than 30 beat/minute. 
  • The lying (supine) heart rate is usually normal or slightly raised.
  • Blood volume is usually reduced (5-25%).
  • Lying plasma norepinephrine (NE) is high normal.
  • Standing plasma NE level is usually elevated. Standing plasma NE levels greater than 2000 pg/ml have been encountered and such patients much be carefully studied to rule out pheochromocytoma.

 

Heterogeneity in POTS

It is likely that the causes of OI are heterogeneous. Potential pathophysiological mechanisms include:

 

  • Partial autonomic neuropathy,
  • Excessive venous pooling,
  • Gravity-dependent fluid shift,
  • Diminished plasma volume or red cell mass,
  • Cardiac beta-adrenergic hypersensitivity,
  • Diminished cardiovagal baroreflex sensitivity,
  • Brainstem dysfunction,
  • Enhanced baseline sympathetic activity.  

 

It is suggested that the finding of abnormally enhanced sympathetic drive to the cardiovascular system is a final common pathophysiological mechanism in the majority of patients.

 

Several patient subgroups have contributed to our understanding of the pathophysiology. These include:

 

 

 

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