Autonomic Disorders
Autonomic Disorders
What You'll Learn
- Neurogenic OH: ΔHR/ΔSBP <0.5 bpm/mmHg (validated) or HR rise <15 bpm despite large BP drop (bedside heuristic) = inadequate baroreflex → think MSA, PAF, diabetic neuropathy, amyloidosis
- POTS (2015 HRS): sustained HR rise ≥30 bpm in adults (≥40 bpm in adolescents) within 10 min of standing/tilt + orthostatic symptoms + absence of orthostatic hypotension. (A standing HR >120 may occur but is NOT a stand-alone criterion.) Young women, often post-viral.
- PAF vs MSA (heuristic, not standalone): both are α-synucleinopathies. Very low supine NE (fails to rise) suggests postganglionic failure (PAF); preserved supine NE with poor standing rise supports preganglionic/central failure (MSA). Interpret with autonomic testing, MIBG, exam, and longitudinal motor/cognitive signs.
- AAG: anti-ganglionic AChR antibodies (α3 nicotinic) — the ONE validated autoimmune autonomic antibody; titer correlates with severity
- Valsalva Phase IV: absent BP overshoot = sympathetic adrenergic failure — most tested autonomic reflex
- Autonomic dysreflexia: SCI above T6 + noxious stimulus below lesion → hypertension + bradycardia — medical emergency
- Preganglionic neurotransmitter: ALL autonomic preganglionic fibers use ACh at nicotinic receptors (sympathetic AND parasympathetic)
HighYield Pearls
- OH definition: SBP ↓≥20 or DBP ↓≥10 within 3 min of standing — memorize the threshold
- Neurogenic vs non-neurogenic OH: neurogenic = BP drop WITHOUT compensatory HR rise (failed baroreflex) → MSA, PAF, PD, diabetic, amyloid, AAG
- POTS criteria (2015 HRS): sustained HR rise ≥30 bpm (≥40 bpm in adolescents) within 10 min of standing/tilt + orthostatic symptoms + absence of orthostatic hypotension; standing HR >120 is NOT a stand-alone criterion
- Pheo BP management: α-blockade FIRST (phenoxybenzamine/doxazosin) — never β-blocker first (unopposed α → hypertensive crisis)
- Autonomic dysreflexia (SCI ≥T6): severe HTN + headache + sweating/flushing above lesion + bradycardia → 1) sit upright, loosen constrictive clothing; 2) monitor BP frequently; 3) search trigger (bladder FIRST, then bowel, skin, other); 4) if SBP persistently ≥150 or markedly above baseline → short-acting antihypertensive (nitroglycerin paste, captopril, hydralazine, carefully administered immediate-release nifedipine per protocol). Avoid sublingual nifedipine.
- AAG antibody: anti-ganglionic AChR (α3 nicotinic) — subacute pandysautonomia (cholinergic + adrenergic failure); treat IVIG/PLEX/rituximab
- PAF (Bradbury-Eggleston): α-synucleinopathy with pure autonomic failure — may convert to PD/DLB/MSA over years
- MSA autonomic clue: early severe OH + urogenital failure + inspiratory stridor + parkinsonism/cerebellar = MSA
- Diabetic autonomic pentad: gastroparesis + erectile dysfunction + OH + asymptomatic hypoglycemia + silent MI
- Supine HTN in neurogenic OH: treat with short-acting agent at bedtime; never use long-acting antihypertensives
🔍 Quick ReferenceClinical / phenotype · Testing · Treatment
Clinical phenotype
- Young woman + palpitations/lightheadedness/brain fog on standing + HR↑ → POTS
- Early severe OH + inspiratory stridor + parkinsonism/cerebellar → MSA
- Slowly progressive pure autonomic failure WITHOUT motor/cognitive features → Pure Autonomic Failure (Bradbury-Eggleston)
- Subacute pandysautonomia (cholinergic + adrenergic) → Autoimmune Autonomic Ganglionopathy (AAG)
- Episodic HTN + headache + palpitations + diaphoresis + tremor → Pheochromocytoma
- SCI ≥T6 + severe HTN + flushing/sweating above lesion + bradycardia → Autonomic dysreflexia
- Gastroparesis + ED + OH + silent MI + asymptomatic hypoglycemia → Diabetic autonomic neuropathy
- Small fiber + autonomic + cardiomyopathy + GI + macroglossia → Amyloid autonomic neuropathy (TTR or AL)
- Sicca + sensory neuronopathy + autonomic failure → Sjögren autonomic ganglionopathy
- Ophthalmoplegia + ataxia + areflexia + autonomic instability → Miller Fisher / GBS variant
Testing / labs
- Tilt-table: BP drop WITHOUT HR rise → Neurogenic OH
- Tilt-table: sustained HR rise ≥30 bpm (≥40 bpm in adolescents) within 10 min + symptoms, NO orthostatic hypotension → POTS (2015 HRS)
- Valsalva Phase IV: absent BP overshoot → Sympathetic adrenergic failure
- Low supine NE (does not rise on standing) → supports postganglionic failure (PAF) — heuristic, not standalone; correlate with autonomic testing / MIBG / exam
- Preserved supine NE with inadequate rise on standing → supports preganglionic/central failure (MSA) — heuristic, not standalone
- Anti-ganglionic AChR (α3 nicotinic) antibody → AAG
- ↑ Plasma free metanephrines / 24-h urine metanephrines → Pheochromocytoma
- Congo red apple-green birefringence on biopsy → Amyloid autonomic neuropathy
- Reduced HR variability on deep breathing / R-R interval → Cardiovagal (parasympathetic) failure
- QSART / TST anhidrosis pattern → Sudomotor (postganglionic sympathetic) failure
Treatment / pearls
- Midodrine (α1 agonist) → Neurogenic OH first-line pressor
- Droxidopa (NE precursor) → Neurogenic OH (PAF, MSA, PD)
- Fludrocortisone (mineralocorticoid) → Volume expansion in OH
- Pyridostigmine → Mild OH — augments residual sympathetic ganglionic transmission
- Phenoxybenzamine / doxazosin BEFORE β-blocker → Pheochromocytoma (avoid unopposed α)
- Increased salt + fluids + compression + recumbent-to-upright exercise → POTS first-line
- Low-dose propranolol / ivabradine → POTS rate control
- IVIG / PLEX / rituximab → AAG
- Sit upright, loosen clothing, monitor BP; search trigger (bladder FIRST, then bowel/skin); if SBP ≥150 or markedly above baseline → short-acting antihypertensive (nitro paste, captopril, hydralazine, careful IR nifedipine per protocol — NOT SL nifedipine) → Autonomic dysreflexia
- Abdominal binder + HOB elevation + avoid hot environments → Non-pharmacologic OH bundle
- Short-acting antihypertensive at bedtime only → Supine HTN in neurogenic OH
Autonomic Nervous System — Quick Review
Sympathetic vs Parasympathetic
| Feature | Sympathetic | Parasympathetic |
|---|---|---|
| Origin | T1–L2 (intermediolateral cell column) | Cranial (III, VII, IX, X) + Sacral (S2–S4) |
| Preganglionic fiber | Short; ACh at nicotinic receptors | Long; ACh at nicotinic receptors |
| Postganglionic fiber | Long; norepinephrine (except sweat glands = ACh) | Short; acetylcholine (muscarinic receptors) |
| Ganglia | Paravertebral (sympathetic chain) + prevertebral (celiac, superior/inferior mesenteric) | Near or within target organ |
| Heart | ↑ HR, ↑ contractility (β1) | ↓ HR, ↓ conduction (muscarinic M2) |
| Pupils | Mydriasis (dilator pupillae, α1) | Miosis (sphincter pupillae, M3) |
| GI | ↓ Motility, sphincter contraction | ↑ Motility, sphincter relaxation |
| Bladder | Detrusor relaxation (β2/3), sphincter contraction (α1) | Detrusor contraction (M3), sphincter relaxation |
| Sweat glands | Eccrine: sympathetic cholinergic (ACh, muscarinic) | No innervation |
Key Anatomic Points
- Adrenal medulla: modified sympathetic ganglion — preganglionic fibers synapse directly; releases epinephrine (80%) + norepinephrine (20%)
- Sympathetic sweat glands: the ONE exception — sympathetic postganglionic fibers that release ACh (not NE)
- Horner syndrome pathway: 3-neuron arc — 1st order: hypothalamus → C8–T2 ciliospinal center of Budge (intermediolateral column); 2nd order: ciliospinal center → superior cervical ganglion (passes over lung apex); 3rd order: SCG → along ICA → cavernous sinus → eye via long ciliary nerves
- Vagus nerve (CN X): provides ~75% of all parasympathetic innervation; heart, lungs, GI (to splenic flexure)
💎 Board Pearl
- ALL preganglionic fibers (sympathetic AND parasympathetic) use ACh at nicotinic receptors — this is why ganglionic AChR antibodies cause pandysautonomia
- Sympathetic postganglionic = NE everywhere EXCEPT sweat glands (ACh, muscarinic) — classic board question
Orthostatic Hypotension
Definition & Criteria
- Orthostatic hypotension: SBP drop ≥20 mmHg OR DBP drop ≥10 mmHg within 3 minutes of standing (or head-up tilt)
- Initial OH: transient drop within 15 seconds of standing (not sustained) — benign
- Delayed OH: BP drop after 3 minutes but within 10 minutes — may be early neurogenic OH
Neurogenic vs Non-Neurogenic OH
| Feature | Neurogenic OH | Non-Neurogenic OH |
|---|---|---|
| ΔHR / ΔSBP ratio (validated primary criterion) | <0.5 bpm/mmHg | >0.5 bpm/mmHg |
| HR response to standing (supportive bedside heuristic) | <15 bpm rise despite large BP drop | >15 bpm rise (appropriate) |
| Supine NE | Low (PAF) or fails to rise on standing (MSA) | Normal |
| Causes | MSA, PAF, PD, diabetic neuropathy, amyloidosis, AAG | Dehydration, hemorrhage, medications, adrenal insufficiency, sepsis |
| Supine hypertension | Common (loss of baroreflex modulation) | Uncommon |
| Valsalva Phase IV | Absent overshoot | Normal overshoot |
Common Medications Causing OH
- Antihypertensives (α-blockers, diuretics), dopaminergic agents (levodopa, dopamine agonists), TCAs, antipsychotics, nitrates, PDE5 inhibitors
Supine Hypertension
- Defined as SBP ≥140 and/or DBP ≥90 mmHg while supine
- Present in >50% of neurogenic OH patients — makes treatment challenging
- Management: elevate head of bed 10–15° (~6–9 inches), avoid supine position during day, low-dose transdermal nitroglycerin patch at bedtime (removed in AM)
Treatment of Orthostatic Hypotension
| Approach | Intervention | Mechanism / Notes |
|---|---|---|
| Non-pharmacologic | Compression stockings (waist-high) | Reduces venous pooling; abdominal binders more effective than stockings alone |
| Increased salt (6–10 g/day) + fluid (2–3 L/day) | Volume expansion; first step always | |
| Counter-pressure maneuvers | Leg crossing, squatting, muscle tensing during symptoms | |
| Head-up tilt sleeping (10–15°) | Reduces nocturnal supine hypertension + natriuresis; preserves morning volume | |
| Pharmacologic | Midodrine | α1-agonist; peripheral vasoconstriction; avoid within 4 h of bedtime (supine HTN); do NOT give supine |
| Droxidopa (Northera) | Norepinephrine precursor; FDA-approved for neurogenic OH; converted to NE by DOPA decarboxylase | |
| Fludrocortisone | Mineralocorticoid; volume expansion + ↑ vascular α-receptor sensitivity; watch K+, edema, supine HTN | |
| Pyridostigmine | AChE inhibitor; enhances ganglionic transmission; modest effect; less supine hypertension |
💎 Board Pearl
- HR increase <15 bpm on standing = neurogenic OH (baroreflex failure) — the single most important bedside clue
- Droxidopa is the only FDA-approved NE precursor for neurogenic OH — know the drug name
- Midodrine is an α1-agonist — last dose ≥4 hours before bedtime to avoid supine hypertension
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