IS THE INTERSTITIUM REALLY A NEW……ORGAN?
“We propose a revision of the anatomical concepts of the submucosa, dermis, fascia, and vascular adventitia, suggesting that, rather than being densely-packed barrier-like walls of collagen, they are fluid-filled interstitial spaces.
In sum, we describe the anatomy and histology of a previously unrecognized, though widespread, macroscopic, fluid-filled space within and between tissues, a novel expansion and specification of the concept of the human interstitium.” The research team of physicians and scientists from New York University’s Mount Sinai Beth Israel Medical Center (quoted from Seth Augenstein’s article, Discovery of Interstitium Fluid: Does it Upend Human Biology?)
It’s been awhile since I’ve seen medical research (or PRESS RELEASE as is often the case) that’s not touting some new drug, garner as much hype in the mainstream media as Tuesday’s study, Structure and Distribution of an Unrecognized Interstitium in Human Tissues. In order to understand what this study actually says, the first thing we must do is to understand what the interstitial space and interstitial fluid are.
As you might suspect, the fluid contained in the interstitial space is the interstitial fluid. But what’s the interstitial space? the word itself means “empty” or “fragmented,” so basically it’s the ’empty’ space that lies outside the cells, between the capillary walls and CELL MEMBRANE.
Bear in mind that about 2/3 of the body’s fluid is found inside the cells (intracellular fluid), while the remaining third is found outside the cells (extracellular fluid). Most of the extracellular fluid is “interstitial,” while the remaining extracellular fluid is found as blood plasma, cerebrospinal fluid, the gel in your eyeballs, etc, etc. Why do you need to know about interstitial fluid (IF) to understand today’s study? Follow along.
- INTERSTITIAL FLUID PRESSURE IS CRITICAL FOR HOMEOSTASIS: When it comes to health, HOMEOSTASIS is everything. A quick look at PubMed shows study after study intimately correlating various aspects of one’s health with IF pressure.
- INTERSTITIAL FLUID IS THOUGHT TO BE THE CHI (QI) IN ACUPUNCTURE: The January issue of the Chinese Journal of Integrative Medicine (Understanding Qi Running in the Meridians as Interstitial Fluid Flowing Via Interstitial Space of Low Hydraulic Resistance) stated that, “Pathological changes of qi, blood and meridians may lead to discomfort and disease. Treatment with acupuncture or herbal medicine aims to regulate qi and blood so as to recover normal function of the meridians. This paper explores the nature of qi as well as compares and correlates them with the structures of the human body. We propose a conceptualization of qi as being similar to the interstitial fluid, and the meridians as being similar to interstitial space of low hydraulic resistance in the body. Hence, qi running in the meridians can be understood as interstitial fluid flowing via interstitial space of low hydraulic resistance.” Considering you can purchase acupuncture “point finders” for less than 100 bucks that measure electrical resistance, their conclusions make sense and should be fairly simple to prove.
- INTERSTITIAL FLUID AND pH: The February 2015 issue of the World Journal of Diabetes (Roles of Interstitial Fluid pH in Diabetes Mellitus: Glycolysis and Mitochondrial Function) showed just how important MITOCHONDRIAL FUNCTION is as related to both Interstitial Fluid and YOUR BODY’S pH. “The pH of body fluids is one the most important key factors regulating various cell function such as enzyme activity and protein-protein interaction via modification of its binding affinity. Therefore, to keep cell function normal, the pH of body fluids is maintained constant by various systems. Insulin resistance is one of the most important, serious factors making the body condition worse in diabetes mellitus. I have recently found that the pH of body (interstitial) fluids is lower [acidic] in diabetes mellitus than that in non-diabetic control, and that the lowered pH is one of the causes producing insulin resistance. This review proposes perspective therapies on the basis of regulation of body fluid pH including propolis (honeybee product) diet.” Sickness and disease generally require an ACIDIC ENVIRONMENT.
- INTERSTITIAL FLUID “CLEANS” THE CEREBROSPINAL FLUID: Although I found lots of studies on this topic, one from Neurologia Medico-Chirugica (Research into the Physiology of Cerebrospinal Fluid Reaches a New Horizon: Intimate Exchange between Cerebrospinal Fluid and Interstitial Fluid May Contribute to Maintenance of Homeostasis in the Central Nervous System) said it best. “Cerebrospinal fluid (CSF) plays an essential role in maintaining the homeostasis of the central nervous system. The functions of CSF include: buoyancy of the brain, spinal cord, and nerves; volume adjustment in the cranial cavity; nutrient transport; protein or peptide transport; brain volume regulation through osmoregulation; buffering effect against external forces; signal transduction; drug transport; immune system control; elimination of metabolites and unnecessary substances; and finally cooling of heat generated by neural activity. Furthermore, the relationship between the behaviors of CSF and interstitial fluid in the brain and spinal cord is important. In this review, we will introduce functions that were recently discovered such as CSF production and absorption, water molecule movement in the interstitial space, exchange between interstitial fluid and CSF, and drainage of CSF and interstitial fluid into both the venous and the lymphatic systems.” A study from last month’s issue of Biological Psychiatry (The Emerging Relationship Between Interstitial Fluid-Cerebrospinal Fluid Exchange, Amyloid-β, and Sleep) showed more of this relationship as it relates to aberrant physiology and common disease processes.
- INTERSTITIAL FLUID PRESSURE IS ALWAYS HIGH IN TUMORS / CANCER: Part of the hubub surrounding the Interstitium has to do with its relationship to CANCER. A 2014 issue of Cancer Management and Research said this of IF pressure in tumors. “As cancer progresses, a dynamic microenvironment develops that creates and responds to cellular and biophysical cues. Increased intratumoral pressure and corresponding increases in interstitial flow from the tumor bulk to the healthy stroma is an observational hallmark of progressing cancers.” Doctors are concerned about this because this high pressure inside of tumors not only prevents CHEMOTHERAPY DRUGS from reaching their target area, but pushes cancer-containing fluids through the interstitial fluid and lymphatics where it can metastasize and spread.
- INTERSTITIAL FLUID AFFECTS FIBROBLASTIC ACTIVITY: The sac-like compartments of the Interstitium are lined with fibroblasts (cells that create collagen). Last September’s issue of Biochemica et Biophyisica Acta (Interstitial Fluid Flow-Induced Growth Potential and Hyaluronan Synthesis of Fibroblasts in a Fibroblast-Populated Stretched Collagen Gel Culture) concluded that, “Fibroblasts in tensioned collagen gels altered their phenotypes in a MF rate-dependent manner.” In other words, the pressure / flow of the Interstitial Fluid affected FIBROBLASTIC ACTIVITY (which can be either very good or very bad, depending on the situation). HERE are my articles on hyaluronan (aka hyaluronic acid) as well.
- INTERSTITIAL FLUID IS LOADED WITH POTENTIAL BIOMARKERS: Study after study after study talked about using the Interstitial Fluid for its biomarkers (something that Dr. Eric mentioned on the FUNCTIONAL MEDICINE board just yesterday). Why is this such a big deal? The IF will probably present a far closer picture to what’s actually going on with one’s physiology and homeostasis than blood will. A few of these studies looked at CYTOKINES in children with skin conditions, IF tumor biomarkers, and even mRNA, although the list was almost unlimited.
Despite the fact that I could have come up with many others, should we be surprised at this last bullet point? Listen to what the study’s lead author says of this phenomenon. “This finding has potential to drive dramatic advances in medicine, including the possibility that the direct sampling of interstitial fluid may become a powerful diagnostic tool.” The truth is, we are already there, although the technology is not such that it can be accomplished quickly and inexpensively. Until that day comes, blood will continue to be the diagnostic fluid of choice.
HOW WAS THIS “NEW” ORGAN DISCOVERED?
“This tissue system was originally filmed in vivo and described in a number of papers and books by French surgeon Dr Jean-Claude Guimberteau, described on YouTube by Gil Hedley as peri-fascial membranes, and written about by me in Anatomy Trains.
This system can be dubbed a new organ system if you wish, but it is part of a continuous Biomechanical Auto-Regulatory System (which I’ve been talking about for a while) – we could call it that – that runs in a continuous mechanical linkage from the DNA through the nuclear membrane via the microtubules to the cellular membrane, out through the transmemiranous proteins to the glycocalyx (the first mucousy layer outside the cell) to this interstitium and on up to the more gross and dissectible fascial structures.” From an article that came out today after I first published this article (Interstitium: A Statement from Tom Myers)
Firstly, members of the Fascia Research Group in Ulm, have been talking about this phenomenon or something extremely similar for a very long time. Honestly, this discovery sort of reminded me of the “discovery” of the PRIMO-VASCULAR SYSTEM a number of years ago Secondly, since tissue slides are typically dried or looked at in vitro (not in a living body or natural living conditions), the tiny sacs of fluid that make up the Interstitium were never seen because they were always collapsed and empty.
If not viewed in living conditions, the sacs that make up the Interstitium flatten out and appear as fissures or cracks. After using new techniques to view these sacs in vivo (in life), they were seen for what they really are, and are now believed to contain over 15% of one’s total body mass, 20% of one’s total body volume — between 2.5 and 3 gallons of fluid — and are being touted not only as a new organ, but as the largest organ.
The sacs themselves are made up of tissues we’ve talked about on this site many a time, COLLAGEN, and ELASTIN — tissue types that create both strength and elasticity. This allows the sacs to act as fluid reservoirs, as well as shock absorbers / cushions.
What’s doubly cool, however, is that the study’s lead author, pathologist, professor, and stem cell researcher, Neil Theise, has gone on record to state his belief the tissue structures that make up the walls of the sacs actually generate electricity as they flex, elast, bend, and move, due to the pumping action of organs and muscles move (this “pumping” will occur on some level as long as you are alive, but will function much better if you aren’t sedentary). In similar fashion to DR. LANGEVIN, Dr. Theise believes this helps provide an explanation for the reason that acupuncture works.
Where exactly is the Interstitium found? It’s just underneath the mucosal layer in tissues such as FASCIA, SKIN, and according to a Tweet by Theise, “the submucosae of all visceral organs“. The study itself says this. “We observed similar structures in numerous tissues that are subject to intermittent or rhythmic compression, including the submucosae of the entire gastrointestinal tract and urinary bladder, the dermis, the peri-bronchial and peri-arterial soft tissues, and fascia.”
Oh, and if that isn’t enough for you, the interstitium’s fluid is also believed to be the source of LYMPH, as well as containing immune system cells that had never been seen before. Listen as the authors summarize.
“We observed similar structures in numerous tissues that are subject to intermittent or rhythmic compression, including the submucosae of the entire gastrointestinal tract and urinary bladder, the dermis, the peri-bronchial and peri-arterial soft tissues, and fascia… If there is communication between the gut lumen and the submucosal space, this raises the possibility that cell signaling (including hormonal or immunologic signals) could be regulated in a proximal-to-distal manner determined by the speed of peristalsis. Immunologic interactions in this interstitial space could also be important in inflammatory conditions…
Our findings necessitate reconsideration of many of the normal functional activities of different organs and of disordered fluid dynamics in the setting of disease, including fibrosis and metastasis. A submucosa subjected to directional, peristaltic flow is not the previously envisaged wall of dense connective tissue, but a potential conduit for movement of injurious agents, pro-fibrogenic signaling molecules, and tumor cells.
This raises the possibility that direct sampling of the interstitial fluid could be a diagnostic tool. Finally, our study demonstrates the power of in vivo microscopy to generate fresh insights into the anatomy and physiology of normal and diseased tissues.”
I’ve already shown you that diseased tissue changes its fluid dynamics, increasing it’s pressure and tending to create both swelling / edema and FIBROSIS (the medical word for SCAR TISSUE). You also know that fascia is an ORGAN OF MECHANORECEPTION & KINESTHETIC SENSE. In fact, fascia expert, Dr. Robert Schleip, has not only said that fascia probably contains more sensory receptors than the eye (the organ long believed to be the heaviest-innervated), but has shown that vast numbers of these sensory receptors are found in the interstitial space (they are called — you guessed it — “Interstitial Receptors”).
Summarizing Schleip’s work, the TENSEGRITY BLOG (Myofascial Mechanoreceptors) said this of Interstitial (interstitium’s) Mechanoreceptors.
“The Interstitial sisters. Type III and IV mechanoreceptors. The most abundant sensory receptors in the human body. More numerous than the sum of the sensory receptors in the eyes, nose, mouth, ears and skin, including all Type I and Type II fascial mechanoreceptors. Yeah, they’re kinda important! The interstitial receptors are found just about everywhere, including inside our bones! The highest concentration of these are in the periosteum, on the outer surface of bones.
They respond to rapid and sustained pressure changes. 10% are Type III, low threshold pressure units, covered in a thin myelin sheath. They respond to the lightest of feather touches. Type IV receptors are unmyelinated high threshold pressure units, making up the other 90%. Stimulating the Interstitials are known to create change in vasodilation and the autonomic functions, such as blood pressure, heart rate, respiration, salivation and perspiration.
We’re still trying to understand the full impact of these receptors in the body. Some are pain receptors and others are also thought to inform the sensations of structural positioning and movement. Acupuncture is thought to engage these receptors, snagging them in the subtle twisting of the needle.”
When you get down to brass tacks; because fascia (UNDER ITS MANY NAMES) is the tissue that creates the interstitial space, it’s important to know something about it if you want to help people with chronic dysfunctions, CHRONIC PAIN, or even chronic disease. That’s right; thanks to research like this, there is a growing body of researchers who believe that disruptions in the body’s fascial system is the cause of all disease.
That was not a misprint folks — that was all as in all. Because much fascial dysfunction is not simply due to mechanical injury, but instead due to the effects of chronic inflammation, it would behoove you to see what it might take to diminish your body’s inflammatory load (HERE).
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