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HTML Rev: Sept. 26, 1999
Diane Manhattan

Created: May 1998
Diane Manhattan
HTML: August 1998
Nancy Kalanta


You are here: IC Network > Interstitial Cystitis Book-By G. Sant >Chapter 11: The Role Of Glycosaminoglycans In Normal Bladder Physiology And The Patho-Physiology Of Interstitial Cystitis

Chapter 11: The Role Of Glycosaminoglycans In Normal Bladder Physiology And The Patho-Physiology Of Interstitial Cystitis

By: Robert E. Hurst, Johnny B. Roy, and C. Lowell Parsons
  • The bladder epithelium (prevents the resorption of solutes) is a membranous cellular tissue that helps cover the bladder wall from absorption of bacteria from the urine, therefore causing a defense against bacterial colonization.
  • The epithelium covers the area of the bladder and the kidney glomerular membrane (capillaries that act as a filter of blood).
  • The bladder cavity/lumen is covered with the GAG (proteoglycan and glycoprotein). This layer is a thick strong layer that in normal circumstances acts as a antibacterial defense.
  • IC bladders seem to be more absorptive then the normal bladder and IC patients tend to respond to treatments of exogenous sulfated polysaccharides (Elmiron or Heprin) the GAG model has emerged. This approach affirms that the bladder proteoglycan splay a major role in maintaining the impermeability and the deficiency of the GAG as related to the etiology of 60% - 70% of IC patients.
  • Studies done recently show that the membrane itself may suggest an interactive and interdependent system involving the proteoglycan layer and the lipid layer and the tight junctions. (proteoglycan = a conjugated protein of high molecular weight that is found in connective tissue) (lipid = the chief structural components of a living cell)

Structure of Proteoglycan And Glycosaminoglycans.

This section of this chapter describes in great detail the structure of the GAG lining.

The GAG is divided into 4 families on the basis of structure and function. They are as follows:

Structure

  • Heprins and Heprin Sulfates
  • Chondroiton and dermatan
  • hyaluronate
  • keratin sulfates

There are three functional cellular surfaces regarding the epithelial structure, they are as follows:

  • Basallamina or basement membrane surface
  • the cell to cell contact surface within the epithelium
  • the Luminal (the cavity)

The basal lamina plays an active role in the biology of the overlying cellular layer. The basement membrane stores and binds heparin- binding growth factors for the stimulating growth of the overlying cell layers. Biglycan is distributed on cell to cell surfaces and possibly regulates and helps maintain the growth in the epithelium.


Proteoglycans Of The Bladder Luminal Surface.

Little is known about the proteoglycans of the luminal layer of the bladder, even though it has bee mentioned that it was important to the defenses of the bladder against the bacterial adherence and secondly for the role of maintaining bladder surface impermeability. Dr. Parsons and his colleagues used animal studies to show the main evidence for a role of anti-adherence.

The studies showed that not only when they use diluted acids (HCI) for treatment removes some components of the Luminal surface, but also damages the bladders defense against bacteria adherence. But it was also noted that when the damaged bladder was treated with exogenous sulfated polysaccharides(Heparin) it restores the anti-adherence activity.

Another study done by Dr.Parsons, shows 'increased bladder permeability to urea and potassium ions' (pg. 96) It was noted in 70% of IC patients, but when treated with exogenous glycosaminoglycans, such as heparin, 50% of the 70% of IC patients noticed that alleviated symptoms and also noticed that it helps restore the bladders impermeability. Also, studies done with mouse autoimmune cystitis model of IC showed that changes in the permeability also accompany the development of Cystitis. So, this can lead to the consideration that damage to the bladder, regardless to the cause within the deeper tissues of the bladder can lead to chronic injury, irritation and pain but also to degeneration of the bladder.

One study that was also done on examination by microscopic examination, included 108 IC patients. Biopsies were taken and showed a loosely adherent urothelium with frequent patches that have been peeled off, suggesting that fragility of the urothelium from frequent damage is a feature of interstitial cystitis' (page 96) The next two pages of this chapter discuss other studies relating to the GAG


Our Acknowledgements

With gratitude to Grannum Sant for his relentless advocacy for IC patients throughout the world and to Craig Percy (LR) for graciously allowing the ICN to review this book in depth. We would also like to thank all those who have volunteered their time, in making this book an important asset to the IC community around the world. We encourage the purchase of this exceptional book.




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