Why you need to care about the Glycocalyx Model paradigm.

Last weekend many hundreds of people read my last Post on FluidPhysiology about measuring the endothelial glycocalyx, thankyou so much. Starling physiology has grown to become a Controversy, thanks to the misinterpretations published by Professor Robert Hahn and his colleagues in the past year or so. These prompted Professor Charles Michel, Professor Roy Curry and my (not a professor) self to attempt to set the record straight by giving clinicians a detailed explanation of the ways in which the Starling principle is extended. We invited Professor Hahn to respond in the interests of balance and respect for a competing viewpoint, see The Extended Starling principle needs clinical validation

In this year’s Annual Update in Intensive Care and Emergency Medicine Professor Hahn was invited to offer a Contrary view to “a multitude of pro articles claiming a clinical importance for the revised Starling and glycocalyx principles.” The Professor is referring, I expect, to the Glycocalyx model, also called the Michel-Weinbaum model. Entitled “Do Intensivists need to care about the revised Starling principle?“, perhaps I should offer some reasons why Intensivists and others DO need to care about it. I could find little in Hahn’s discussion of glycocalyx pathophysiology that I can disagree with, and am not sure that he is really being Contrary! I think that our differences are about interpreting the data, and are actually very small.

Here I offer a Table, based on the one I published in 2012, summarising the points of difference between a paradigm for prescribers based on pre-extension Starling physiology and a paradigm based on the Michel-Weinbaum model. At the top, notice that Professor Hahn now not only acknowledges the presence of a significant intravascular glycocalyx volume as I described, he has published papers measuring it! Look the Table over again, I’d love to hear what you think. Which strikes you as having the most clinical relevance?

Original Starling principle paradigmExtended Starling principle or Glycocalyx Model paradigm.
Intravascular volume consists of plasma and cellular elements.Intravascular volume consists of glycocalyx volume, plasma volume, and cellular elements.
Capillaries separate plasma with high protein concentration from interstitial fluid (ISF) with low protein concentration. Sinusoidal tissues (marrow, spleen, and liver) have discontinuous capillaries and their interstitial fluid (ISF) is essentially part of the plasma volume.
Open fenestrated capillaries produce the renal glomerular filtrate. 
Diaphragm fenestrated capillaries in specialized tissues can sustain absorbtion of ISF to plasma. 
Continuous capillaries exhibit ‘no absorption’.
The endothelial glycocalyx is semi-permeable to proteins and their concentration in the intercellular clefts below the glycocalyx is low.
The important Starling forces are the transendothelial pressure difference and the plasma–interstitial colloid osmotic pressure difference operating across a porous endothelial barrier. The important Starling forces are the transendothelial pressure difference and the plasma – subglycocalyx colloid osmotic pressure difference operating across the continuous glycocalyx.
Fluid is filtered from the arterial end of capillaries and absorbed from the venular end, while small proportion returns to the circulation as lymph.Transendothelial solvent filtration (Jv) is much less than predicted by Starling’s principle, and the major route for return to the circulation is as lymph.
Raising plasma colloid osmotic pressure with hyper osmotic colloid solutions enhances absorption and shifts oedema fluid from ISF to plasma. Raising plasma colloid osmotic pressure reduces Jv but does not cause sustained absorption of ISF and is not a sufficient treatment of oedema.
Auto transfusion after abrupt disequilibrium is a transient phenomenon, and limited to about 500 ml.
At subnormal capillary pressure, net absorption increases plasma volume. At subnormal capillary pressure, Jv approaches zero. 
Auto transfusion after abrupt disequilibrium is a transient phenomenon, and limited to about 500 ml.
At supranormal capillary pressure, net filtration increases ISF volume.At supranormal capillary pressure, when the colloid osmotic pressure difference is maximal, Jv is proportional to transendothelial pressure difference 
Infused colloid solution is distributed through the plasma volume, and infused isotonic salt solution through the extracellular volume. 100 ml of isosmotic colloid is equivalent to 400 ml of crystalloid for its contribution to plasma volume.Infused colloid solution is initially distributed through the plasma volume, and infused isotonic salt solution through the intravascular volume. The effect on plasma volume is context-sensitive.
At supranormal capillary pressure, infusion of colloid solution preserves plasma colloid osmotic pressure, raises capillary pressure, and increases Jv.
Infusion of isotonic salt solution also raises capillary pressure, but it lowers colloid osmotic pressure and so increases Jv more than the same colloid solution volume.
At subnormal capillary pressure, infusion of colloid solution increases plasma volume and infusion of isotonic salt solution increases intravascular volume, but Jv remains close to zero in both cases. 100 ml of isosmotic colloid is equivalent to no more than 150 ml of crystalloid for its contribution to plasma volume.
Traditional versus extended Starling principle paradigms for fluid therapy.

Leave a Reply

Your email address will not be published. Required fields are marked *