Question 18

College Answer

a)
The endothelial glycocalyx forms the basal skeleton that in vivo interacts dynamically with plasma
constituents forming an endothelial surface layer (ESL)
 forms the interface between the vessel wall and moving blood
 protein-free space below the glycocalyx
 maintenance of the vascular permeability barrier
 mediation of shear-stress-dependent nitric oxide production
 retention of vascular protective enzymes (e.g. superoxide dismutase)
 retention of coagulation inhibition factors (e.g. antithrombin, the protein C system and tissue
factor pathway inhibitor)
 modulation of the inflammatory response by preventing leukocyte adhesion and binding
various ligands (e.g. chemokines, cytokines and growth factors)

b)
Glycocalyx shedding and disruption is associated with:
 TNFα, redox stress and oxidised lipoproteins,
 ischaemia/reperfusion
 hyperglycaemia, hypernatremia
 hypervolemia,
 trauma, surgery,
 artificial colloids such as hydroxyethyl starch

c)
Effects of glycocalyx damage
 capillary leak
 edema
 hypercoagulability
 inflammation
 loss of vascular responsiveness
 platelet aggregation

Discussion

A more thorough examination of what the glycocalyx is can be found in the Required Reading section.

The college answer is pretty good. That is pretty much everything you can be expect to remember in the ten-minute episode of exam panic dedicated to this question.

An idealised response furnished with references would resemble the following:

a) What is the endothelial glycocalyx? Outline its potential importance in sepsis.

• The glycocalyx is a thin (500-1000nm) hydrated gel-like layer on the luminal surface of the vascular endothelium
• It is composed of a vast variety of macromolecules, including glycoproteins, polysaccharides, proteoglycans, glycosaminoglycans, plasma proteins, enzymes and enzyme inhibitors, growth factors, cytokines, amino acids, cations and water.
• Glycocalyx degradation may be resposible for much of the organ damaged observed in sepsis.
• Concentration of glycocalyx components shed into the bloodstream correlates with sepsis severity.

b) Name factors that can disrupt the endothelial surface layer (ESL).

• Any pathological process that is known to cause atheroma formation:
  • Hyperglycaemia
  • Hyperlipidaemia
  • Smoking
• Inflammation, mediated by TNFα (this is prevented by hydrocortisone)
• Ischaemia-reperfusion injury (which halts the endothelial synthesis of glycosaminoglycan
• Hypervolemia (mediated by actions of the ANP)
• Hydroxyethyl starch ( in same study that investigated the effects of hypervolemia)
• Major vascular surgery (seems like a consequence of bypass and ischaemia/reperfusion)

c) What are the effects of glycocalyx disruption?

• Local hypercoagulability
• Global autoheparinisation (especially during trauma)
• Increased capillary permeability
  • Tissue and organ oedema
  • Impaired microcirculatory oxygen distribution
  • Loss of vascular responsiveness
• Increased platelet aggregation, leading to microvascular thrombosis and DIC
• Increased leucocyte-endothelium interaction, leading to inflammation

A much more complete list of references is available elsewhere.

Those of key importance are:

Reitsma, Sietze, et al. "The endothelial glycocalyx: composition, functions, and visualization." Pflügers Archiv-European Journal of Physiology 454.3 (2007): 345-359.

Burke-Gaffney, Anne, and Timothy W. Evans. "Lest we forget the endothelial glycocalyx in sepsis." Critical Care 16.2 (2012): 121.

Becker, Bernhard F., et al. "Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential." Cardiovascular research (2010): cvq137.

VanTeeffelen, Jurgen W., et al. "Endothelial glycocalyx: sweet shield of blood vessels." Trends in cardiovascular medicine 17.3 (2007): 101-105.

Ait-Oufella, H., et al. "The endothelium: physiological functions and role in microcirculatory failure during severe sepsis." Applied Physiology in Intensive Care Medicine 2. Springer Berlin Heidelberg, 2012. 237-249.

Alphonsus, C. S., and R. N. Rodseth. "The endothelial glycocalyx: a review of the vascular barrier." Anaesthesia 69.7 (2014): 777-784.