Junction Dysfunction Abstract
Abstract
SUMMARY:
The human body functions as a SRCS, adapting to stress through mechanisms like AREs. However, overload from various stressors can lead to JD, causing issues like TCLS and MSS, disrupting vasoadaptation, fluidity, and leading to inflammation, auto-intoxication, and immune system suppression. Addressing dysfunctions at multiple levels is necessary to restore the SRCS homeostasis and complete WHCs.
ABSTRACT:
Similar to other living organisms, the human body acts as a Self-Reorganizing Complexification System (SRCS). This means all components of the body have the ability to work together to adapt to stressful challenges. Normally during stressful challenges, adaptive mechanisms kick in such as Antioxidant Response Enzymes (AREs), in a process called in hormesis.
When this system is overloaded due to unfavorable situations such as xenobiotic exposure, certain pathological structures, and dysfunctional support systems, then cascade loops can entail, sending the system into multiple positive and negative feedback loops. The pathology of Junction Dysfunction (JD), which is what happens when the glycocalyx (the negatively charged, highly sulfated sugar structure that creates a protective barrier on the endothelial, epithelial, and lymphatic lumen layers; as well as surrounding immune cells acting as selective opsonins and dysopsonins) becomes compromised. In JD, consequentially Transient Capillary Leak Syndrome (TCLS) and Micro Sepsis (MSS) are two subpathologies that contribute to the loss of Vaso-Adaptation (VA), the ability (or inability) to handle vasoactive stressors.
TCLS allows for fluids systemically or focally to “leak” - transverse from lumenal spaces to tissue - generally on the (micro) vascular capillary vessels and lymphatic vessels. TCLS on the microcapillary level also causes blood and immune stasis and abnormal vessel channel flow. This “leakage” and “stasis” in TCLS disrupts the mitochondrial saltitory mechanisms and disrupts electrolyte homeostasis (Na/K), leading to hypoxia-response genes, and thus generation of Reactive Oxygen Species (ROS), lactate, and CO2.
TCLS also leads to poor vasoadpatiation via fluid volume and dysautonomic renin/adrenergic signalling. TCLS also creates an environment where immune cells become sticky and senescent. TCLS of the gut’s epithelium leads to dysbiosis and leads to systemic endotoxemia/Endotoxin Looping via the liver’s portal vein further contributing to poor ability to participate in Phase 3 Conjugation.
Lipopolysaccharides’s (LPS) auto-intoxication leads to TLR4 signalling which further exacerbates inflammation in an adaptive response, producing Nitric Oxide (NO), Histamine, and Serotonin: 3 vasodilators and potent immune stimulants. TLR activation + Endotoxemia turns on the inflammasome inducing MSS via canonical and non-canonical pathways. Chronic LPS exposure leads to lipid accumulation, biofilm creation, innate immune system hyperoxidation and immunosuppression and can become systemic, but not limited as focalized infections tend to gather in the areas of most immune suppression such as areas of the body that have been previously injured.
These characteristics are common features of MSS due to NETosis, neutrophil exhaustion, endotoxin tolerance, glycosylated and oxidized lipids/sugars/proteins/debris, and foam cell creation. Hyperoxidation creates continual redox issues thus depleting redox enzymes, while immunosuppression allows for co-infections to accumulate and/or latent infection(s) to express. Suppression of the innate immune system forces the adaptive immune system to take over to clean up the downstream byproducts of Alarmins and the immune system phagocytosis it’s dead tissue via opsoninic antibody production.
Inflammation from inflammasome activation utilizes and depletes the same cofactors used for neurotransmission, Phase 1/2 Detoxification, methylation, and immune tolerance, amongst other factors and functions. Due to poor abundance of cofactors and sticky vessels, there is a much higher chance of bioaccumulating toxins (xenobiotics like glyphosate or mycotoxins and/or endogenous toxins). This creates a feedback cascade for more dysbiosis as co-infections (plus their microbial byproducts) as pathogenic microbes pleomorph in toxic environments feeding off of damaged and more easily habitable decaying/senescent human tissue.
Remodeling of the Extracellular Matrix (ECM) is hindered during this cascade and thus the completion of Wound Healing Cycles (WHC) are not achieved well and eventually remodels poorly. Continuous dysfunction in glycocalyx/ECM remodeling, leakage of cell barriers, accumulation of toxins, biofilm accumulation, and poor redox, making homeostasis harder and harder to achieve as time goes by. Corrective action at most levels need to be addressed in order to get the SRCS functioning, allowing it to fully complete WHCs.
In this series…
In this series, we explore the many common fallacies that are crippling many aspects of conventional, alternative, functional, and foundational healthcare systems. We elucidate on the actionable steps that help bring the body back into a healing state (healthy feedback loops) as to not be chronically ill (caught in derogatory feedback loops).
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