Interstitial Cystitis: Enhancing Early Identification in Primary Care Settings

Brittany N. Heck, FNP, MSN

Disclosures

Journal for Nurse Practitioners. 2007;3(8):509-519. 

In This Article

Pathophysiology

Currently, the underlying pathophysiology of IC and PBS remains unclear. The literature suggests that IC or PBS is the result of a multifactorial process that occurs after an initial insult, such as a urinary tract infection (UTI) or allergic trigger occurring within the bladder.[9] The events in the pathogenesis of IC and PBS are shown in Figure 1.[10] Although several theories have been proposed about the pathophysiology of IC, leading causes are structural, immunologic, and neurogenic factors that result after the initial bladder insult occurs. Over time, continued aggravation of such factors gives rise to the symptoms of urinary urgency, frequency, and pelvic pain.

Figure 1.

Bladder Wall Defect

The healthy bladder contains a mucus lining, the glycosaminoglycan (GAG) layer, that serves to protect the underlying tissues of the bladder from harmful elements within the urine. Research investigations have focused on a key concept about the pathophysiology of IC and PBS and a defect within the GAG layer. Patients with IC or PBS were found to display an increased permeability within the urothelium that allows urinary contents to pass into the underlying tissues and cause damage.[11] In addition, potassium, which is present in increased amounts within urine, was identified as playing a critical role in this process. Specifically, the increased diffusion of potassium into the underlying tissues causes chronic inflammation, tissue injury, mast cell degranulation, and depolarization of nerve fibers.[9] Over time, progressive damage to the bladder occurs, leading to urinary urgency, frequency, and pelvic pain. Recent findings from Parsons et al[12] show that patients with IC or PBS have lower ratios of potassium to creatinine in the urine, supporting the theory of a permeability defect leading to increased potassium diffusion.

Mast Cell Activation

Mast cells, which play a key role in the inflammatory process, have also been identified in the development of IC and PBS. Mast cells contain granules of histamine, leukotrienes, and prostaglandins, which are responsible for stimulation of the inflammatory response.[13] Patients with IC or PBS have an increased number of mast cells within the bladder walls.[14] However, it is unclear whether this serves as a primary or secondary cause of injury. Research also suggests that when bladder insult occurs, mast cells are activated and release their granules, causing degranulation into the nearby tissue. This degranulation triggers an inflammatory response, thereby causing smooth muscle contraction, local tissue damage, and the stimulation of nerve fibers.[15] Over time, these events promote further damage to the GAG layer of the bladder wall.

Neurogenic Inflammation

Neurogenic inflammation occurs when sensory nerves release inflammatory mediators into the surrounding tissue, resulting in pain and local inflammation.[13] The role of substance P, an inflammatory mediator located within sensory nerves, is of critical importance in this process. Patients with IC or PBS exhibit an increased amount of substance P-containing nerve fibers, located directly beneath the bladder interstitium.[16] Nerve stimulation, specifically in relation to mast cell degranulation, causes the release of substance P to enter the surrounding tissue. The inflammatory effects of substance P within the tissue results in sustained inflammation and increased activation of nerve endings.[9] Prolonged activation of substance P on the nerve endings results in a decrease in the amount of stimuli needed to induce symptoms of IC and PBS. Therefore, the progression of symptoms is augmented even under small amounts of bladder insult.

Antiproliferative Factor

Another working theory is that antiproliferative factor (APF), a protein found within the urine of patients with IC or PBS, may also play a role in the underlying pathophysiology. Keay et al[17] isolated APF within the urine of 94% of patients diagnosed with IC or PBS, as compared with 9% in patients without this diagnosis. APF damages the bladder in patients with IC or PBS by inhibiting the normal growth of epithelial cells, while simultaneously decreasing the amount of epithelial growth factor within the urine.[9] The coexistence of these two processes impedes proper regeneration of damaged areas within the bladder and increases the risk of more injury or insult to occur. Although some data suggest that the presence of APF may be indicative of IC and PBS, not enough evidence supports the use of APF as a viable definitive diagnostic tool.

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