Endothelial Glycocalyx

Front 1

What is the endothelial Glycocalyx

Back 1

The glycocalyx is a complex gel layer that coats all healthy vascular endothelium. This layer exists in dynamic interaction between flowing blood and the endothelial cell wall. It plays a pivotal role in vascular protection, modulation and haemostasis.

Front 2

What is the endothelial Glycocalyx composed of?. 2.

Back 2

Glycoproteins and proteoglycans.

Front 3

How do proteoglycans differ?

Back 3

They differ in size,

number of GAG side chains

& whether they attach to the cell membrane or not.

Front 4

Name the types of Proteoglycans? .2

Back 4

Those that First bind to cell membrane & attach Gags later

syndecans & glypicans

Those that First Bind GAG & then r secreted by the endothelial cell.

perlecans, mimecans, biglycans, decorins & versicans.

Front 5

Describe the structure of Proteoglycans

Back 5

Proteoglycans have a protein core to which are attached negatively charged glycosaminoglycan (GAG) side chains.

Front 6

List the 5 types of GAG side chains

Back 6

Heparin 50-90%

Hyluronic acid: the only GAG NOT bound to a core protein & forms viscous solutions with water.

Dermatin

Chondroitin

Keratin

Front 7

What is the function of Glycoproteins within the Endothelial Glycocalyx? .2.

Back 7

1. act as adhesion molecules and contribute to the coagulation, fibrinolytic and haemostatic systems. These include E and P selectin which are expressed after stimulation by histamine, thrombin, interleukin-1 and tumour necrosis factora (TNF-α).

2. Ligands for leucocyte and platelet adhesion ICAM-1, ICAM-2, VCAM-1, PECAM-1 are also expressed within the glycocalyx.

Front 8

Describe the Sieve effect / function of the Endothelial Glycocalyx?

Does Albumin permeate the Glycocalyx? Explain.

Back 8

The charged mesh of the glycocalyx acts as a macromolecular sieve, repelling negatively charged molecules, as well as white and red blood cells and platelets. Macromolecules larger than 70 kDa are excluded from the glycocalyx.

Albumin is 67 kDa and thus leaks through the glycocalyx despite its mostly negative charge. However it does also carry positive charge, and this amphoteric nature helps it to also bind to the glycocalyx. This binding reduces the hydraulic conductivity across the vascular barrier

Front 9

What is the role of the Endothelial Surface Layer & how is it formed.?

Back 9

The ESL regulates vascular

permeability,

influences blood cell-vessel wall interactions,

affects rheology

and controls the microenvironment.

The binding of plasma constituents to the inert framework of glycocalyx produces the physiologically active endothelial surface layer (ESL)1

Hint 9

Rheology = deformation & flow of a fluid.

Front 10

Starling Principle. How has this been revised?

Back 10

Front 11

List the three components of starling equation that were revised.

Back 11

1.Sustained venous reabsorption does not occur in most tissues, only in specialized tissues like the kidney and intestines. And Lymphatic drainage is low.

2. Capillary filtration rate is much less than Starling predicted.

Why is the capillary filtration rate it less than Starling predicted? And how is this possible?

3) The endothelial surface layer reduces hydraulic conductivity. Oncotic forces are only set up across the endothelial surface layer on the luminal aspect of the endothelial cell, not across the whole capillary wall. Capillary filtration rate is tightly regulated. The oncotic pressure differences across the endothelial surface layer reach equilibrium very quickly, thereby leading to less fluid filtration.

Front 12

What are the pathological process that affect glycocalyx integrity, cause shedding & disruption?

Back 12

1) Ischaemia/reperfusion

2) Sepsis

3) Volume loading

4) Hyperglycaemia

5) Atherosclerosis

6) Trauma/cardiac and aortic bypass surgery

Front 13

What are the effects of Shedding of Glycocalyx.? 5.

Back 13

- capillary leak

- oedema

- accelerated inflammation

- platelet aggregation

- hypercoagulability - loss of vascular responsiveness

Front 14

Why is it difficult to assess the Glycocalyx?

Back 14

The glycocalyx is a difficult structure to visualize because it is destroyed by conventional dyeing and fixation techniques. Dynamic assessment of the glycocalyx is also difficult and current technologies are not readily available

Front 15

Examples of Novel technology that can assess the endothelial glycocalyx.

Back 15

current technologies are not readily available and can only assess the glycocalyx in easily assessible parts of the circulation, eg. sublingual microcirculation. These novel technologies are: Orthogonal polarization spectral imaging (OPS) and side-stream dark field imaging (SDF).

Front 16

List therapies that may provide benefit to the endothelial glycocalyx.

Back 16

-Avoiding hyperglycaemia

-Albumin

-Steroids in septic shock

-Sevoflurane

-Avoiding hypervolaemia

-Statins Therapies such as TNF inhibition, antithrombin III and infusions of glycocalyx constituents are still experimental.

Front 17

What is the role of the Endothelial Glycocalyx in:

A. Immunity

B. Fertilization

C. Embryonic development.

Back 17

A. Defense against cancer: Changes in the glycocalyx of cancerous cells enable the immune system to recognize and destroy them. Inflammation regulation: Glycocalyx coating on endothelial walls in blood vessels prevents leukocytes from rolling/binding in healthy states.

B. The spermatozoa glycocalyx is a dynamic coating of extracellular glycoproteins known to facilitate the acrosome reaction and fertilization in mammals

C. Included in the glycocalyx are cell-adhesion molecules that enable cells to adhere to each other and guide the movement of cells during embryonic development

Front 18

List 3 elements of the Glycocalyx.

Back 18

proteoglycans (PG), glycoproteins bound with sialic acid, glycosaminoglycans (GAG), and associated plasma proteins [

Front 19

Explain the Glycocalyx as a mechano-transducer

Back 19

Front 20

Role of glycocalyx in the BBB.

Back 20

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