Fluid Therapy and the Glycocalyx
Clinical reserach supports that traditional fluid therapy results in substantial diminution and damage to the glycocalyx. Data suggests that management of the Glycocalyx and Endothelium at the onset of Inflammatory Response is critical to reduction in morbidity.
•The glycocalyx allows some laminar flow of blood cells in its intimate relationship with the endothelial cells of the vascularity.
•A noxious injury occurs to the Glycocalyx layer of the endothelium of the capillaries. Known mechanisms of injury are shock, endotoxins, hypovolemia, burns, absent pulsatile flow, reperfusion and other causes.
•Loss of or damage to the glycocalyx exposes the endothelial cells surface and inflammation causing cytokine release. Icam1, Vcam1, Il-6, TNFalfa, H-hscp, P-E1F2alfa, AtF6 protein are some of the known sites.
•Vascular tone seems to be regulated by NO receptors in the capillaries.GRP78 protein leads to Actin; CHOP protein expression leads to Actin: GRP78To GAPDH is a gene sequence expression of these cells. ( The Glue Grant data showed m-RNS did not control the inflammatory process.) More data about the Glycocalyx and the endothelial cells is rapidly accumulating.
The human inflammatory response is the response to injury that alters the homeostatic physiology of the human body. Just as the insult is varied so is the response to the injury also varied in intensity. The responses range from minimal to the devastating “Cytokine Storm” leading to Multiorgan failure and death. Current medical interventions are only supportive.
The glycocalyx is damaged by many different sources, The rate and severity of the damage to the glycocalyx cannot be measured today. The multiple factors present on the surface of the endothelial cells cause the varied systems of the inflammatory to become activated and begin to create the damage to the human body. The different patterns of Multiorgan Failure that have recently been described relate to the organelle site that has been most exposed. The glycocalyx is a plasma layer that covers the endothelial cells and covers the activators of the inflammatory response. During the healthy circulation this layer provides a barrier between the platelets and the white blood cells and the red blood cells and preventing inflammatory activation. In the initiation of the inflammatory cascade, the loss or damage to this glycocalyx layer allows damage to the platelets or the white blood cells, and the triggered inflammatory cellular response results.
In animal studies given a large dose of an inflammatory endotoxin the extracellular fluid leak was not affected and the disease process progressed rapidly to the experimental study of inflammatory death. This is a pattern of Cytokine Storm
However, early introduction limited third spacing in sepsis with peritonitis other cases of sepsis also had very modified clinical courses of illness.
Application in later stages of fluid overload with anasarca resulted in a measurable increase in the serum albumin and mobilization of the fluid.
Review of the limited data did suggest a very different mechanism of activity.
The very electrically charged glycocalyx is a very dynamic organ. One pattern of destruction is the total loss of the glycocalyx allows the massive stimulation of the inflammatory cascade or the Cytokine Storm. The mechanism can be total coagulation and total loss of the protective layer.
However lesser destruction can also be present ranging from agglutination to clumping due to surface tension . This concept allows variable amounts of exposed endothelial surface and the “clumping”can allow different patterns of exposure.
In summary the noxious stimuli, alters the slimy plasma glycocalyx layer to allow exposure of the surface of the endothelial cells that contain the multiple factors that begin the inflammatory cascade.
The progression from the first exposure to massive destruction of the entire glycocalyx and full exposure can allow the development of different patterns of multiorgan failure that are clinically observed.
The Solution?
Dr. William Norberg hypothesized that a larger, protein rich albumin molecule might be the answer to fluid-shift. He formulated a combination of human serum albumin and hydrolyzed amino acids in normal saline - “The Norberg Solution” or “TNS”. The initial mechanism of TNS action was purported to be a 17% larger molecular size and this new size was larger than the endothelial pore size of 67000 Daltons and therefore the fluid shift was attributed to the TNS obstructing the pores and causing the fluid shifts as proposed by the Starling Principle.
With greater experience, more effects were noted. In many cases the albumin continued to increase despite no further infusions. The benefits seemed to persist much longer than anticipated. Additionally, subjectively the disease process seemed to be diminished. Early use has indicated TNS is effective in clearing the anasarca of Multiorgan failure and appears to limit third spacing fluid loss is trauma and sepsis. No other drug or product has more than a minor benefit in the support of the glycocalyx. In the applied series TNS seems to alter and seems to repair and re-establish the Glycocalyx layer and its function. Further study is needed. However, studies, and early clinical use as detailed in case reports, supports this hypothesis.
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