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Orthostatic Hypotension:causes, mechanisms, and influencing factors

Christopher J Mathias, DPhil, FRCPNeurology 1995; 45:S6-S11

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Control of Blood Pressure

• autonomic nervous system

• heart’s resistance and capacitance

• intravascular volume

• hormones– renin-angiotensin-aldosterone system– aldosterone– local endothelin or nitric acid

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Orthostatic hypotensionconsensus definition (1)

• reduction of – systolic BP of at least 20 mm Hg, or– diastolic BP of at least 10 mm Hg

within 3 minutes of standing (some may

take more than 10 minutes)

• similar drop in blood pressure within 3 minutes in a head-up tilt table test at an angle of at least 60 degrees

1. Neurology 1996; 46:1470

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Orthostatic hypotension

“when associated with relevant symptoms indicating impaired perfusion, a smaller drop in blood pressure may be equally important, especially for further investigation.”

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Orthostatic hypotensionsymptoms

• symptoms develop on assuming the erect posture– lightheadedness, dizziness, blurred

vision, weakness, fatigue, cognitive impairment, nausea, palpitations, tremulousness, headache, neck ache

• some patients may be asymptomatic

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Autonomic Nervous SystemNeurogenic causes of

orthostatic hypotension

• Primary autonomic failure

• Secondary autonomic failure

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Primary autonomic failure

• chronic– pure autonomic failure– Shy-Drager syndrome• with parkinsonian features• with cerebellar and pyramidal features• with multiple system atrophy (combination)

• acute or subacute dysautonomias

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Secondary autonomic failure

• central

• spinal

• peripheral

• miscellaneous

• drugs

• neurally mediated syncope

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Secondary autonomic failure1. central

• brain tumors, especially of the 3rd ventricle or posterior fossa

• multiple sclerosis

• syringobulbia

• age-related

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Secondary autonomic failure2. spinal

• spinal transverse myelitis

• transverse myelitis

• syringomyelia

• spinal tumor

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Secondary autonomic failure3. peripheral

• afferent

– Guillain-Barre syndrome, Tabes dorsalis, Holmes-Adie syndrome

• efferent

– diabetes mellitus, amyloidsis, surgery, dopamine-b-hydroxylase deficiency

• afferent / efferent

– familial dysautonomia (Riley-Day synd)

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Secondary autonomic failure4. miscellaneous

• autoimmune and collagen disorders

• renal failure

• neoplasia

• human immunodeficiency virus infection

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Secondary autonomic failure5. drugs

• centrally acting – clonidine, methyldopa, reserpine,

barbiturates, anesthetics

• peripherally acting– guanethidine, bethanadine– phenoxybenzamine, prazosin– propranolol, timolol

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Secondary autonomic failure6. neurally mediated syncope• vasovagal syncope

• carotid sinus hypersensitivity

• micturition syncope

• glossopharyngeal neuralgia and syncope

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Neurogenic orthostatic hypotensionpathophysiology

• major abnormality is the lack of neurally mediated vasoconstriction in large vascular beds (skeletal muscle and the splanchnic bed)

• gravitational pooling in the periphery with lack of compensatory change

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Plasma norepinephrine level

• measure of sympathetic activity

• in neurogenic OH, the sympathetic nervous system is not activated, the rise in NE level is minimal or absent despite a marked fall in BP

• basal NE level cannot determine the site of lesion

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Rise in plasma norepinephrine after 10 min Head-up tilt to 450

050

100150200250300350400450500

Controls MSA PAF DBH

Supine

Tilt

Nor

adre

nal

ine

(pg/

mL

)

Multiple system atrophy

Pure autonomic failure

Dopamine ß-OHdeficiency

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Nonneurogenic causesof hypotension

• cardiac impairmentmyocardial impaired ventricular filling

impaired output cardiac arrhythmia

• vasodilatation

• low intravascular volumeblood / plasma loss fluid / electrolytes

• miscellaneous

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Nonneurogenic Hypotension1. cardiac impairment

• myocardialmyocarditis, myocardial infarction

• impaired ventricular fillingatrial myxoma, constrictive pericarditis

• impaired outputaortic stenosis, hypertrophic cardiomyopathy

• cardiac arrhythmiabradycardia, tachydysrhythmias

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Nonneurogenic Hypotension2. vasodilatation

• drugs-nitrates

• alcohol

• heat, pyrexia

• hyperbradykinism

• systemic mastocytosis

• extensive varicose veins

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Nonneurogenic Hypotension3. low intravascular volume

• Blood / plasma losshemorrhage, burns, hemodialysis

• Fluid / electrolyteinadequate intake (anorexia, vomiting)

diarrhea (including ileostomy)

renal/endocrine (salt losing nephropathy,

Addison’s, diabetes insipidus, diuretics

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Nonneurogenic Hypotension3. miscellaneous

• Sepsis

• Endotoxic shock

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Factors influencingpostural hypotension

• speed of positional change

• prolonged recumbency

• time of day (morning on rising)

• warm environment (hot weather, central heating, hot bath)

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Factors influencingpostural hypotension

• food and alcohol (1)

• physical exertion (2)

(bending forward, abdominal compression, leg crossing, squatting)

• increased intrathoracic pressure(micturition, cough, defication)

1. Mathias CJ, et al. 1992; Autonomic Failure2. Smith GDP, et al. 1993; BHJ 1993; 69:359-361