Interstitial Cystitis - Causes

Causes

The cause of IC/BPS is currently unknown, however, several explanations have been proposed and include: autoimmune theory, nerve theory, mast cell theory, leaky lining theory, infection theory, and a theory of production of a toxic substance in the urine. Other suggested etiological causes are neurologic, allergic, genetic, and stress-psychological. In addition, recent research shows that IC patients may have a substance in the urine that inhibits the growth of cells in the bladder epithelium. An infection may then predispose those patients to develop IC. Current evidence from clinical and laboratory studies confirms that mast cells play a central role in IC/PBS possible due to their ability to release histamine and cause pain, swelling, scarring, and interfere with healing. Research has shown that there is a proliferation of nerve fibers present in the bladders of IC patients which is absent in the bladders of people who have not been diagnosed with IC.

Regardless of the origin, it is clear that the majority of IC/BPS patients struggle with a damaged urothelium, or bladder lining. When the surface glycosaminoglycan (GAG) layer is damaged (via a urinary tract infection (UTI), excessive consumption of coffee or sodas, traumatic injury, etc.), urinary chemicals can "leak" into surrounding tissues, causing pain, inflammation, and urinary symptoms. Oral medications like pentosan polysulfate and medications that are placed directly into the bladder via a catheter sometimes work to repair and rebuild this damaged/wounded lining, allowing for a reduction in symptoms. Most literature supports the belief that IC's symptoms are associated with a defect in the bladder epithelium lining allows irritating substances in the urine to penetrate into the bladder — essentially, a breakdown of the bladder lining (also known as Adherence Theory). Deficiency in this glycosaminoglycan layer on the surface of the bladder results in increased permeability of the underlying submucosal tissues.

GP51 has been identified as a possible urinary biomarker for IC with significant variations in GP51 levels in IC patients when compared to individuals without interstitial cystitis.

Numerous studies have noted the link between IC, anxiety, stress, hyperresponsiveness, and panic. Another proposed etiology for interstitial cystitis is that the body's immune system attacks the bladder. Biopsies on the bladder walls of people with IC usually contain mast cells. Mast cell containing histamine packets gather when an allergic reaction is occurring. The body identifies the bladder wall as a foreign agent, and the histamine packets burst open and attack. The body attacks itself, which is the basis of autoimmune disorders. Additionally, the idea has been put forward that IC is triggered by an unknown toxin or stimulus which causes nerves in the bladder wall to fire uncontrollably. When they fire, they release substances called neuropeptides that induce a cascade of reactions that cause pain in the bladder wall.