Can we measure the endothelial glycocalyx?

This month we read an interesting experiment by Sweden’s Robert Hahn, an attempt to quantify the intravascular volume that is not the free-flowing plasma we sample by venesection or by drawing from an intravascular catheter. https://icm-experimental.springeropen.com/articles/10.1186/s40635-020-00317-z

We have to thank Fitz-Roy Curry in California for much of our current knowledge about the structure and function of the microvasculature.

This diagram from a 2017 Editorial nicely shows the current knowledge. Red blood cells are separated from the bare endothelial cell membrane by an inner-layer of membrane-bound proteins that act as a barrier to the passage of albumin and other plasma proteins and an outer layer with plenty of hyaluronan.

Two layered endothelial glycocalyx.

The current model of the endothelial glycocalyx describes an inner dense matrix layer, associated with membrane-attached glycoproteins (up to 200–300 nm thick) that forms a primary selective barrier to plasma macromolecules, and an outer less dense layer that may extend one or more microns into the vessel lumen, and forms a micro-structure that supports red cell move- ment through microvessels and restricts inflammatory cell access to the endothelial cell surface. The whole glycocalyx barrier is in series with the transendothelial pathways for water and solutes through the inter- endothelial junctions and specialized transendothelial pathways via vesicles and fenestrations.

Curry FE 2017

There are no bright line boundaries, and the volume of water within the glycocalyx layer is continuously adjusting according to the velocity of blood flow, intravascular pressure and inflating pressure. At no-flow the layer is deflated. Hahn’s approach to quantify the “water volume hidden within the glycocalyx [is to compare] the tracer techniques used to estimate the blood volume versus a population kinetic analysis of crystalloid fluid. The rationale is that red blood cells are excluded from the glycocalyx, whereas an infused fluid volume will penetrate into this layer.” Hahn acknowledges all the limitations of any attempt to measure the glycocalyx volume. Not least is the error attached to each measurement that becomes enormous error after combining the measurements necessary to calculate the volume we want to estimate. Even so, I applaud and welcome this contribution because it educates clinicians about the whole-intravascular volume advantage of crystalloids over colloids for resuscitation from hypovolaemia. An important read for Starling Physiology-aware doctors.

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