Bidirectional flow in the fine veins

[Cece]

https://www.sciencedirect.com/science/a ... 771930386X

A physics derived explanation for what having blocked jugular veins does to the blood vessels of the brain

[Trevortucker]

Thank you for citing this cerebrospinal venous flow paper Cece. There is a second paper also scheduled for publication in Medical Hypotheses which addresses the impact of vortex flow on valves and intraluminal growths like webs and septa in the major veins in the thoracic cavity. The abstract is at https://www.sciencedirect.com/science/a ... 7719300672.

[Cece]

That's a new idea in the second paper. Rather than saying the bad valves cause bad flow, you are saying the bad flow may be causing bad valves and septum and etc. It's not even bad flow precisely but vortex flow that would be naturally occurring when the jugulars encounter a junction with a larger vein? This vortex flow would happen in everyone's veins at those locations and in some unlucky people, but not everyone, it would result in the intraluminal abnormalities?

The previous idea on the bad valves etc was that they were congenital in origin. The existence of fetal veins (that would normally close up before birth) through the skull that persist into adulthood was a bit of evidence in favor of the idea that the blood flow was dysfunctional prior to birth, so the fetal veins did not close as they normally would since they were still needed.

If MS patients' jugular veins have a wide variety of abnormalities, then some of it could be congenital, others developing later on, including as a result of this vortex flow at the junctions. The two ideas aren't necessarily in competition but could be cumulative.

Thank you for continuing your work on this.

[Trevortucker]

You captured the premise precisely. The venous malformations in MS appear to be similar to atherosclerosis (artery) malformations which are now widely accepted to be related to low and reversing blood flow shear stress. (ie hardening of the veins.)

[Cece]

I did a site search here and this is the first time we've discussed vortex flow using the phrase "vortex flow" although reflux seems to be the same concept.

I found a good breakdown of the differences between laminar flow, turbulent flow and vortex flow:
http://mriquestions.com/laminar-v-turbulent.html
Turbulent flow is fast, vortex flow is slow and going the wrong direction.

Vortex flow refers to localized swirling or stagnant blood flow that has separated from the central streamlines within a vessel. Such vortices, also called flow eddies, frequently occur at vascular bifurcations and distal to areas of stenosis.

When it says that vortex flow occurs at vascular bifurcations, that would fit with what was said about vortex flow occuring at the junction of the veins, such as subclavian and jugular or jugular and brachiocephalic.

I checked back for who it was who was looking at cadaver samples of IJVs from MS patients and found that there was a shift in collagen from collagen 1 to collagen 3. It was Gabbiani who worked closely with Zamboni: https://www.ncbi.nlm.nih.gov/pubmed/22770861

Cheerleader talked about one of Gabbiani's early talks in 2009: viewtopic.php?f=40&t=10680&p=212229&hil ... +3#p212229

Dr. Lee makes a comment...
This collagen conversion from I to III happens in the arteries had no idea it could happen in the veins as well!

Again though this difference in collagen is believed to be genetic and developed in utero.
viewtopic.php?p=212169#p212169

Zamboni believes that The collage problem is genetic and present in utero. I recall a paper that showed that the gene for this problem resides on same chromosome as some of the MS markers.

Edited to add: never mind, the collagen abnormalities are irrelevant to this. They occur throughout the vein, not specifically in the junction areas. It's the endothelial layer that's relevant and the intraluminal abnormalities.

https://www.omicsonline.org/open-access ... ?aid=63610

Intraluminal defects are considered one of the main mechanisms causing a significant delay of jugular flow in course of chronic cerebrospinal venous insufficiency (CCSVI), when investigated by an objective standardized catheter venography method [42]. Recently the ultrastructure of the intimal layer of the IJV of MS patients have been investigated by the means of scanning electronic microscopy (SEM) [43].

Control vein showed a virtually intact endothelial layer, with regular disposition of the cells (Figure 5). This appearance changed completely in the diseased specimen, displaying areas of partially detached endothelial cells and the loss of the integrity of the luminal monolayer as evidenced by craters or cavities (Figure 5).

The picture resembles chronic venous insufficiency of the lower limb where the endothelial cells are found detached and irregularly disposed mirroring flow turbulences characterized by a disorder of velocity and flow direction [44].

https://www.ncbi.nlm.nih.gov/pubmed/15568038

Lab Invest. 2005 Jan;85(1):9-23.
The role of shear stress in the pathogenesis of atherosclerosis.
Cunningham KS1, Gotlieb AI.
Author information
Erratum in
Lab Invest. 2005 Jul;85(7):942.
Although the pathobiology of atherosclerosis is a complex multifactorial process, blood flow-induced shear stress has emerged as an essential feature of atherogenesis. This fluid drag force acting on the vessel wall is mechanotransduced into a biochemical signal that results in changes in vascular behavior. Maintenance of a physiologic, laminar shear stress is known to be crucial for normal vascular functioning, which includes the regulation of vascular caliber as well as inhibition of proliferation, thrombosis and inflammation of the vessel wall. Thus, shear stress is atheroprotective. It is also recognized that disturbed or oscillatory flows near arterial bifurcations, branch ostia and curvatures are associated with atheroma formation. Additionally, vascular endothelium has been shown to have different behavioral responses to altered flow patterns both at the molecular and cellular levels and these reactions are proposed to promote atherosclerosis in synergy with other well-defined systemic risk factors. Nonlaminar flow promotes changes to endothelial gene expression, cytoskeletal arrangement, wound repair, leukocyte adhesion as well as to the vasoreactive, oxidative and inflammatory states of the artery wall. Disturbed shear stress also influences the site selectivity of atherosclerotic plaque formation as well as its associated vessel wall remodeling, which can affect plaque vulnerability, stent restenosis and smooth muscle cell intimal hyperplasia in venous bypass grafts. Thus, shear stress is critically important in regulating the atheroprotective, normal physiology as well as the pathobiology and dysfunction of the vessel wall through complex molecular mechanisms that promote atherogenesis.

If shear stress is this problematic in the arteries, it stands to reason it could be problematic in the veins as well.

[Cece]

https://www.omicsonline.org/open-access ... ?aid=63610

From Zamboni on the pathology of the IJV:

Stuck, immobile valve leaflets were observed in clinical practice on MS patients in course of catheter venography, external and intraluminal ultrasound [2,7,32]. The clinical imaging mirrors the cadaveric study of Diaconu. It would be expected that a congenital TVM should be lined by something like a single flattened layer of endothelial cells surrounded by sparse, irregularly distributed SMCs. When defective valves were observed at SEM, the more surprising finding was the absence of endothelial cells in the examined specimen. In addition, a reticular and fibrotic lamina replaced the endothelial layer. This finding opens, of course, new questions about the origin of defective valves.

This is from 2015 with Zamboni finding an unexpected absence of endothelial cells and presence of reticular and fibrotic lamina in the valves. This is not what would be expected if it was congenital. So that opens to the door to other noncongenital explanations.

[Trevortucker]

The content of the two papers is encapsulated in the abstract for a presentation I made at ISNVD in Ferrara a few weeks ago, as follows:

"Fluid Dynamics of Venous Flow in Multiple Sclerosis
Trevor Tucker (PhD)
Abstract
Background
Venous insufficiency in multiple sclerosis (MS) has often been associated with immobile valves in the tributary veins of the brachiocephalic veins (BVs) and the superior vena cava (SVC). Immobile valves have, in turn, been associated with reflux pulse flow in the tributary internal jugular (IJV), azygous (AV) and vertebral veins (VVs), causing breakdown of the blood-brain barrier (BBB) and extravasation of lymphocytes into the cerebral parenchyma.
Methods
The physics of fluid dynamics is used to analyze the transition from laminar to localized chaotic flow in the BVs and SVC as represented by compliant, curved tubes with flow confluences. Chaotic flow particularly includes vortices, stagnation points and periodic reversing flow. Fluid dynamics is also applied to analyzing reflux flow patterns and standing pressure waves in the IJVs, AV, VVs and deep cerebral veins (DCVs).
Results
For typical venous structures of the BVs, SVC, IJVs, AV and VVs, fluid dynamics predicts localized vortex generation with periodic reversing flow and points of flow stagnation at curvatures, at tributary flow confluences with the BVs and SVC and at valve leaflets proximal to the confluences. Such chaotic flow is associated with the development of venosclerosis plaques at such points. This analysis predicts plaque formation and valve immobility most prominently in the left IJV, secondarily the right IJV and tertiarily in the AV and VVs as observed in clinical trials. Vortex generation is also associated with valve leaflet elongation and the growth of flaps and septa as observed clinically. Standing wave patterns in the IJV, AV and VVs, which are dependent on venous compliances, are predicted to cause stagnant and periodic reversing flow in the DCVs, resulting in disruption of the blood-brain barrier, also as observed clinically.
Conclusions
Applying fluid dynamics to flow transition from laminar to chaotic in compliant tubes with curves and confluences provides substantial insight into the causality of vein scleroses and subsequent disruption of the BBB in MS."

[Cece]

How was it received at ISNVD? Did you get any useful feedback?

It also seems to me that, for it to be venosclerosis, then it is not a variant of normal, but it is actually abnormal. Early on some of the abnormalities were dismissed as within the vast normal spectrum seen for veins. But venosclerosis is a disease process which makes it abnormal.

[Trevortucker]

It seems to have been well received, in that quite a number of audience members were taking pictures of the slides as I presented them. It was presented in a brief format on the second stage, not the main stage, with perhaps 30 to 40 in attendance. There were no questions after the presentation, but that evening, the feedback, expressed over the gala’s dinner table seated with a number of senior medical people from various hospitals and with different specializations, was it should have had a spot on the main stage, and the concept of the malformations being primarily flow-related rather than embryonic was a new insight worthy of more research. I was gratified with the interest and response it received.