Hydraulic and Vascular Autonomic Dysregulation in POTS- The Modified Geddes Baroreceptor Hypothesis

Dr Graham Exelby May 2025

Abstract

Postural Orthostatic Tachycardia Syndrome (POTS) reflects a multifactorial disruption of vascular, hydraulic, and autonomic regulation, best explained by a modified baroreceptor hypothesis integrating venous obstruction, brainstem hypoperfusion, and neuroimmune activation.

Building on the foundational work of Geddes et al., this paper proposes a unified framework wherein preload dysfunction, intracranial venous congestion, and carotid baroreceptor distortion interact to destabilize autonomic balance. Central to this model is the recognition that obstructive phenomena—particularly at the C1 internal jugular junction, thoracic outlet, and vertebral venous plexus—impede cerebrovascular and glymphatic clearance, elevate intracranial pressure, and mislead baroreceptor signalling.

The resulting dysregulation of brainstem perfusion, compounded by hypoxia-induced RAGE/CCL2 activation, fosters a self-perpetuating cycle of sympathetic overdrive, parasympathetic withdrawal, and central sensitization. Mechanical compression of the carotid artery by a distended IJV, dynamic vertebral venous flow restriction, and aberrant CSF drainage via the canalicular system amplify cognitive symptoms, PEM, and orthostatic intolerance. Additionally, postural compromise of middle cerebral artery inflow and venous sinus stenosis explains cerebral hypoperfusion independent of systemic blood pressure shifts.

This vascular-hydraulic model reframes POTS as a condition driven by upstream mechanical and perfusion deficits, rather than isolated autonomic malfunction.  It highlights the need for precision diagnostics (e.g., upright MRI, Doppler flow studies) and multimodal interventions targeting venous outflow, fascial release, metabolic support, and neuroimmune stabilization. Future research should prioritize stratifying POTS phenotypes based on identifiable anatomical and flow-related bottlenecks to improve therapeutic outcomes.

Introduction

The Geddes model of carotid baroreceptor function in POTS (Geddes et al 2024) (1) incorporates both sympathetic and parasympathetic activity, with the balance and sensitivity of these systems contributing to the characteristic symptoms of POTS.  It provides a framework for understanding the complex interplay between these autonomic systems in maintaining cardiovascular homeostasis and how their dysfunction leads to POTS symptoms.

The baroreflex control system maintains homeostasis by regulating blood pressure and heart rate. In this model, the carotid baroreceptors play a crucial role:

1. Afferent signalling: Baroreceptors in the carotid sinus sense changes in blood pressure.

2. Central integration: The signals are integrated in the medulla.

3. Efferent response: Both sympathetic and parasympathetic neurons are activated to modulate the cardiovascular system.

The Modified Geddes Baroreceptor Hypothesis integrates the effects of brainstem hypoperfusion, venous congestion, and preload dysfunction into a unified model of autonomic dysfunction, metabolic instability, and neuroimmune sensitization. This framework reconciles both cardiac overfill and underfill mechanisms in POTS, providing a pathophysiological basis for sympathetic overactivation, HPA axis dysregulation, and neurovascular impairment.

By incorporating preload dysfunction, venous congestion, and dynamic fluid shifts, this model which examines the brainstem hypoperfusion and other vascular dysregulation explains the variability in autonomic compensation, postural intolerance, and neuroinflammatory burden observed in POTS. 

Addressing brainstem perfusion, autonomic rebalancing, and neuroimmune stabilization is essential to breaking the cycle of autonomic and metabolic dysfunction.

This modified model integrates:

• Brainstem hypoperfusion and autonomic instability, with hypoperfusion and immune and inflammatory dysregulation involving the RAGE/CCL2 pathways affecting the Paraventricular Nucleus (PVN) and baroreceptor dysfunction

• Effect of cerebral venous congestion on CSF flow via the arachnoid granulations affecting clearance of toxic waste from the brain via the Glymphatic System

• Vertebral venous congestion and its impact on cerebrovascular outflow

• Dynamic overfill/underfill shifts leading to preload dysfunction contributing to cardiovascular and neuroimmune dysregulation with the potential role of the Azygous System in determining susceptibility to the preload dysfunction

• RAGE-activated microglial and astrocyte neuroimmune activation as a self-sustaining sustaining factor in autonomic dysfunction

Baroreflex Dysfunction and Central Autonomic Dysregulation

Dysfunction in baroreceptor signalling is one of the primary drivers of excess sympathetic activation in POTS. The baroreflex, which normally maintains blood pressure homeostasis, is impaired in many POTS patients, leading to inappropriate autonomic compensation.   The high pressure receptors are found on the Carotid artery bifurcation and aortic arch.   Low pressure receptors are found in the atria and venae cavae.

Mechanical Obstruction of the Internal Jugular Vein causing Autonomic dysregulation

Clinic studies have found internal jugular vein (IJV) obstruction at C1 (stylojugular or venous Eagle or stylohyoid syndrome), from dysfunctional valves in the IJV and from venous Thoracic Outlet Syndrome.(VTOS)  The C1 obstruction causes venous backflow into the cerebral venous system and usually accompanying lymphatic and probably CSF Canalicular System obstruction.    The latter is a new finding and as yet I can find only anatomical details (described in POTS- Mechanical and Hydraulic Drivers.)

The IJV obstructed by dysfunctional or stenotic valves or from the VTOS causes dilatation of the vein in the confines of the carotid sheath which can lead to compression of the carotid artery and accompanying carotid baroreceptors.  

The Role of Internal Jugular Vein and Cervical Vertebral Vein Compression in the Neck

Clinical findings show that in a large number of POTS patients, the internal jugular vein (IJV)—the main vein draining blood from the brain—can become obstructed. The primary source of venous flow from the brain is via the IJV when supine, and the cervical vertebral venous plexus and veins when standing, and this flow difference, and the nearby lymphatics, accounts for most head-related postural symptoms.  This can happen due to:

• IJV compression between the first cervical vertebra (C1) and nearby bony structures (e.g., styloid process or hyoid bone)-Stylohyoid / Stylojugular/ Venous Eagle Syndromes

• Valve abnormalities inside the vein

• Compression from thoracic outlet syndrome (VTOS) as the base of the neck

• IJV obstruction causes blood pressure into the brain and surrounding tissues, leading to venous congestion

• Lymphatics can also be obstructed at C1 or base of neck from VTOS, potentially impairing cerebrospinal fluid (CSF) drainage and impaired glymphatic clearance

• Obstruction at the base of the neck may cause dilatation of the Carotid Sheath in which resides the Carotid Artery and Carotid Sinus and baroreceptors potentially affecting the dysfunctional carotid baroreceptor (from brainstem hypoxia affecting the paraventricular nucleus or PVN)

• When the enlarged jugular vein presses on the carotid artery, this can potentially mislead the baroreceptors into thinking blood pressure is high (when it’s not), prompting inappropriate heart rate or vascular changes.   

• CSF Canalicular system is a newly discovered lymphatic clearance system by Pessa in 2023,(2) that may be obstructed at C1 and base of the neck, amplifying the CSF/ lymphatic flow obstruction from the brain.  At this stage there is only anatomical modelling.

• These may worsen cognitive symptoms, headaches, and postural instability

Vertebral Venous Obstruction in the neck

Dynamic cervical vertebral vein studies in POTS with head pressure symptoms standing have confirmed an overwhelming association with dysfunctional vertebral venous flow.   Some have demonstrated retrograde flow when standing.   Most show significant levels of obstruction with head flexion/rotation, frequently completely obstructed, and the return to normal flow with correction of the postural obstruction is often delayed which could contribute to ICH.    Kosuki et al.2020 (3) using an upright MRI, and Niggerman et al 2010 (4) showed that the vertebral venous plexus at the cervical level was prominent in an erect posture. .  The vertebral venous plexus, which courses along the entire length of the spine, plays a role in the main venous outflow or large-capacity venous reservoir in an upright posture.

The emissary veins at the base of the neck absorbing excess cerebral outflow during vertebral or jugular vein obstruction is well-documented,  These veins act as collateral pathways to alleviate venous congestion and prevent severe ICH, and collaterals bypassing longstanding obstruction may be seen.  

Intra-abdominal venous compression syndromes, such as May-Thurner syndrome or Nutcracker syndrome, have been implicated in venous pooling and secondary congestion of paraspinal, spinal and vertebral systems.(Ormiston et al 2022 (5))   The vertebral system is valveless and Scholbach (6) demonstrated the association of this with Intracranial Hypertension (ICH).(Huang et al. 2023. (7))

Venous Outflow Obstruction and Intracranial Hypertension

Venous congestion is felt to be the commonest cause of ICH.(Karahalios et al 1966 (8)).   Their study suggests that elevated intracranial venous pressure may be a universal mechanism in Idiopathic ICH of different aetiologies.  This elevated venous pressure leads to elevation in CSF and intracranial pressure by resisting CSF absorption.  This was reinforced by Townsend and Fargen 2021 (9) who described Intracranial Hypertension not idiopathic , but that elevated pressure” is consistently and uniformly commensurate with elevations in venous sinus pressures.”(9)

They described pulsatile tinnitus from dysfunctional venous flow in the affected transverse sinus, with this becoming louder with increasing headache from head pressure, and resulting in venous congestion upstream of the stenosis with elevation of venous pressures, thereby resulting in further elevation in intracranial pressure, which could lead to stenosis of the transverse sinus, high intracranial venous pressures upstream of the stenosis, and the clinical signs and symptoms of IIH. This hypothesis is supported by a number of studies comparing pre-and post LP sinus calibres on invasive and non-invasive imaging.” (Jacob, Boisserand et al 2019 (10))  

An over-riding principle on CSF/intracranial venous pressure was described by Townsend and Fargen (9), and a major contribution to the understanding of these hydraulic connections: “Intracranial CSF pressures and intracranial venous pressures are coupled by arachnoid granulations, which exist predominantly in the superior sagittal sinus (SSS).  Animal studies have demonstrated that unidirectional flow of CSF from the subarachnoid space into the venous sinuses through these granulations occurs at a pressure gradient of 3–5 mmHg.”  “As intracranial venous pressure rises, the pressure within the subarachnoid space (ICP) will rise until it is 3–5 mmHg higher than the venous sinus, at which point CSF will drain across the arachnoid granulations. This equilibrium is the basis of the connection between intracranial pressure and venous sinus pressure.”(9)

MRI brain venography frequently showed hypoplastic transverse (and other sinuses).  It is often very difficult to separate anatomical variation from post COVID stenosis.   A common clue are enlarged arachnoid granulations, as the body we believe tries to accommodate the altered venous and CSF pressure.  The venous changes are compounded in COVID by a dysfunctional Glymphatic System, and the importance of the astrocytes whose end feet line the paravascular channels becomes apparent.    Whether persistent flow disruption leads to permanent ICH is a matter of some debate, as clinical trials of a mix of physical with lymphatic therapy has shown significant improvements in symptoms.

 This model provides for the postural variation seen in head pressure in POTS.

Carotid Artery Compression and Progressive Cerebral Hypoperfusion

 Progressive cerebral hypoperfusion in POTS and Long COVID appears to involve impaired flow through the Middle Cerebral Artery (MCA), with emerging evidence pointing to mechanical or positional compromise originating at the carotid and subclavian arteries. Notably, this vascular insufficiency occurs independently of systemic hemodynamic changes, suggesting localized structural or autoregulatory dysfunction rather than pure autonomic failure.

Internal jugular vein (IJV) distension or obstruction, particularly at the venous angle, may exert extrinsic compression on the carotid artery, further diminishing cerebral perfusion. Such interactions could disrupt baroreceptor signalling to the hypothalamic paraventricular nucleus (PVN), compounding central dysautonomia. SPECT imaging corroborates this with demonstrable regional hypoperfusion, indicating that impaired cerebral autoregulation and mechanical compression are plausible convergent mechanisms.

• Impaired Middle Cerebral Artery flow has been described by Wells et al in POTS (11) and van Campen in Long COVID in 2022 (12) These patients exhibit significant reductions in cerebral blood flow via the Middle Cerebral Artery during tilt tests without proportional changes in heart rate or blood pressure, suggesting a primary vascular mechanism rather than purely autonomic dysfunction.

• The dysfunctional Middle Cerebral Artery flow may then be traced  back to the Carotid Artery, then to the Subclavian Artery where there is a strong probability there is a significant postural/ head position underlying cause of the reduced flow whether direct on the artery, or from external compression.  

• Van Campen et al 2018 (13) showed in healthy individuals, tilt testing showed a small but significant reduction in global cerebral blood flow across all four major cerebral arteries, including the internal carotid and vertebral arteries, proportional to orthostatic stress

• In CFS patients, van Campen et al in 2021 (14) showed using tilt testing, a 29% reduction in CBF in tilt testing, with incomplete recovery to normal values post-tilt. This delayed recovery was independent of hemodynamic responses and correlated with disease severity.

• Hermisillo et al 2006 (15) identified abnormal Middle Cerebral Artery flow patterns in POTS patients, including excessive reductions in systolic velocity despite stable arterial blood pressure, suggesting impaired autoregulation or structural factors affecting carotid artery flow.

• In IJV Obstruction at the venous angle  expanded IJV could exert pressure on the carotid artery, potentially reducing its diameter and blood flow.  Studies have shown that jugular vein distension or increased venous pressure can affect neighbouring structures, including the carotid artery. For example, gravitational effects on the neck's venous system during tilt studies show significant changes in IJV cross-sectional area, which could theoretically compress adjacent arteries. (Whittle & Diaz-Artiles 2022. (16))

• This could potentially decrease cerebral perfusion pressure and cerebral blood flow, especially if autoregulatory mechanisms are impaired.

• The postural component here could also implicate the IJV obstruction potentially affecting the carotid artery and the carotid sinus/baroreceptor with signalling to the Paraventricular Nucleus in the hypothalamus.  

• Progressive hypoperfusion has been demonstrated in brain SPECT scans.  The underlying causes remains an area of particular interest.

This vascular hypothesis warrants further investigation, particularly in patients with persistent orthostatic intolerance and neurocognitive decline despite stable systemic parameters.

References

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