Pathophysiology
Clinical meaning
The clinician evaluating orthostatic hypotension must perform comprehensive autonomic nervous system assessment and differentiate the underlying etiology for targeted management. Autonomic function testing includes: cardiovagal function (heart rate response to deep breathing -- normally varies by 15+ bpm; Valsalva ratio normally above 1.5), adrenergic function (BP response to Valsalva maneuver -- Phase II should show minimal BP decline in healthy individuals; Phase IV should show BP overshoot above baseline; absence of Phase IV overshoot indicates impaired adrenergic function), and sudomotor function (quantitative sudomotor axon reflex test QSART -- reduced sweat output indicates postganglionic sympathetic cholinergic dysfunction). The Composite Autonomic Severity Score (CASS) integrates these results into a standardized severity grading (0-10). For neurogenic OH specifically, supine and upright plasma norepinephrine levels are diagnostic: central autonomic failure (MSA, PAF) shows low supine NE (below 100 pg/mL) that fails to rise adequately with standing; peripheral autonomic failure (diabetic, amyloid) shows low supine NE with absent standing increase; intact autonomic system shows supine NE 200-400 pg/mL with doubling upon standing. The clinician prescribes pharmacological therapy, manages the supine hypertension paradox, evaluates for treatable...