Glomerulation

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Glomerulation refers to bladder hemorrhages which are thought to be associated with some types of interstitial cystitis (IC).

Contents

The presence of glomerulations, also known as petechial hemorrhages, in the bladder suggests that the bladder wall has been damaged, irritated, and/or inflamed. Petechial hemorrhages originate from punctuate hemorrhages. [1] The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diagnostic Criteria for IC, developed in 1987, required the presence of glomerulations or Hunner's Ulcers for diagnosis of IC and is still used today, to determine eligibility for some clinical trials. [2] However other research has theorized that the hydrodistention procedure used for the diagnosis of IC itself may have created these tiny broken blood vessels. [3] Studies have found glomerulations in asymptomatic populations, suggesting that they are not applicable as a marker for IC. [4] Thus, a diagnosis of IC is now based upon other, less invasive methods, such as the PUF Scale (Pelvic Pain and Urgency/Frequency Patient Symptom Scale). Glomerulation has been observed to be one of the feature for prostate cancer. [5] However, efforts to determine whether this is association or causation have concluded that while glomerulations may be a common finding in individuals with prostate cancer, they are not a significant predictor. [6]

Presentation

Glomerulations appear as checkerboard/lattice patterns, splotches, or pinpoint-sized red marks on the bladder. [7] [8] Glomerulations are classified into five grades that take into consideration the type and location of injury: Grade 0 (normal mucosa), Grade I (petechiae in at least two quadrants), Grade II (large submucosal bleeding), Grade III (diffuse global submucosal bleeding), and Grade IV (mucosal disruption, with or without bleeding). [9] [10]

According to NIDDK criteria for inclusion in IC studies, examination for glomerulations is performed following hydrodistention of the bladder. In this procedure, water is instilled into the bladder to a pressure of 80–100 cm for 1–2 minutes. When water is drained from the bladder, glomerulations may appear. To be considered as IC, these submucosal hemorrhages must be present in at least 3 quadrants of the bladder with over 10 glomerulations per quadrant. Glomerulations should not be along the path of cystoscope which may suggest trauma instead. [11]

Pathophysiology

The pathophysiologic mechanism of glomerulations is unknown and debated. [4] Some researchers suggest it may be the bladder's response to prolonged periods of underfilling. [12] Another possible mechanism of glomerulation is over expression of angiogenic growth factors in the bladder. [13]

It has been shown that glomerulations are also presented under hydrodistension procedures. [9] During the filling portion of hydrodistension, one can see white fibrous bundles as the bladder is stretched. When stretched, blood flow is interrupted in these fibrous bundles. After this stretching phase, the emptying phase allows blood flow to resume. This is where one can see bleeding from capillaries. [9]

In relation to interstitial cystitis, when noxious stimuli are present, it causes injury to the bladder mucosa resulting in recruitment of inflammatory cells. [3] Disruption of glycosaminoglycan (GAG) layer [14] along with the increased presence of mast cells, T cells, and B cells causes the bladder epithelium to become more permeable. Injury to the GAG layer may lead to increased release of adhesion factors that bind to angiogenic molecules, which generally have little presence under normal conditions, to promote wound healing. Ultimately, increased adhesion factors and overproduction of angiogenic factors from mast cells and disruption of the GAG layer results in tissue fibrosis. [3] As mentioned above, the technique of hydrodistention is one method used to diagnose interstitial cystitis, in which the atrophic bladder is filled and emptied and thus, the stretch of the bladder wall is one possible mechanism of glomerulations. [9]

Risk factors

Diagnosis of chronic pelvic pain or discomfort, accompanied with urinary symptoms, seems to be the most likely risk factor for glomerulation. [9] Research has shown that up to 7.5% of the adult female population is associated with chronic pelvic pain (CPP), in which irritative voiding is commonly seen. Bladder tissue damage is a component that could lead to CPP. These symptoms are also seen in IC which may have led to the pathogenesis of glomerulation through hydrodistention. [15] [3]

It is speculated that chronic underfilling of the bladder contributes to glomerulations. For example, glomerulations can be seen after radiation therapy, in individuals undergoing dialysis, and after urinary diversion. [12]

Relation to interstitial cystitis

The identification of glomerulations as diagnostic criteria for interstitial cystitis/ bladder pain syndrome is unclear. [4] Interstitial cystitis (IC)/ bladder pain syndrome (BPS) is associated with chronic pelvic pain, pressure and discomfort within the urinary system. [16] In 1987, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) developed diagnostic criteria for IC which included the presence of glomerulations or petechial hemorrhages. [2] The purpose of the NIDDK diagnostic criteria was to facilitate comparable groups for research. [17] It was not intended to set strict criteria for the diagnosis of IC.

Interstitial cystitis may also induce angiogenic factors including VEGF (vascular endothelial growth factor) and PD-ECGF (platelet-derived endothelial cell growth factor) resulting in neovascularization. [3] Angiogenic Factors are crucial in vessel development as high values may lead to vessels without enough pericyte coverage. [18] Formation of these newer and weaker vessels in the submucosa associated specifically with IC or BPS, may rupture during hydrodistention causing glomerulation. [3]

In addition to hydrodistension related glomerulations, a study by Rosamilia et al. has shown that biopsied bladders from women with interstitial cystitis have decreased vessel density in the subepithelium. With this, data collected by Irwin et al. also showed that blood perfusion in interstitial cystitis bladders is reduced. Thus, decreased blood perfusion may further increase the expression of angiogenic factors VEGF and PD-ECGF. [9] Alongside with VEGF there is an increase in Hypoxia-inducible factor-1 (HIF-1), for HIF-1 binds to VEGF when oxygen is limited in availability. [19]

Many guidelines do not use glomerulations as a diagnostic criteria for BPS/IC. In a 2014 review of systematic literature searches on PubMed, there were no consistent correlation between the grade or severity of glomerulation and BPS/IC. [4] In the ESSIC guideline, glomerulations are only used to further differentiate bladder pain syndrome (BPS) without Hunner's ulcers into different categories: BPS Type 1 (without glomerulations) and BPS Type 2 (with glomerulations). [20] [16] The American Urological Association guideline mentions that glomerulations may be detected on cystoscopy, but that it is not specific for BPS/IC. [21] High rates of glomerulations have been observed in other urological conditions such as benign prostatic hyperplasia, upper urinary tract stones, prostatitis, etc. which challenges its use as a diagnostic marker. [4]

In fact, signs of interstitial cystitis can expand from glomerulations to Hunner's ulcers and fibrosis. Though one should note that many times, the diagnosis of IC in an individual may not be accurate to the time in which the individual already has IC. Therefore, whether glomerulations are observed during the time of a hydrodistension procedure cannot conclude that it is associated with interstitial cystitis.

Prognosis

Glomerulation can be life-threatening when the rate of blood loss is faster than rate of blood transfusion. Severe bleeding can arise due to IC and bladder carcinoma. [22] In severe bladder hemorrhages, prolonged hospitalization may occur. [23] However, glomerulations can occur in both symptomatic Bladder Pain Syndrome and non-symptomatic Bladder Pain Syndrome. [24]

There is no consistent evidence that glomerulations are correlated to severity of urinary symptoms, quality of life, bladder inflammation, or bladder capacity. [4] One study suggests that the severity of glomerulations may change over time as seen in a few individuals who have either worsened or diminished glomerulations in their subsequent evaluations. [4]

Treatment

Though there is limited research on the treatment of glomerulation, some researchers found that it is safe to implement transcatheter arterial embolization of the prostatic or vesical arteries to sustainably control bladder hemorrhage. It is a minimally invasive procedure with a 90% success rate and is well-tolerated in most cases. It is proven to improve quality of life. [22]

Since there are not many established treatment available, the best treatment for glomerulation is prevention, ex. ensure adequate hydration to flush out infection, beware of drug-induced bleeding and continuous bladder irrigation. [25] [23] In regards to surgery, it has been mentioned that surgery is often the last resort. [26]

In people with interstitial cystitis, guidelines such as the American Urological Association (AUC) and Canada Urological Association (CUA) do not differentiate treatment strategies between those with and without glomerulations. While fulguration is listed as a third-line treatment option for interstitial cystitis with Hunner's Lesions, guidelines do not recommend it to treat glomerulations. [27] Instead, guidelines have set symptom control and quality of life as some of the main goals of treatment for IC. [28] [27] However, there is a lack of consistent evidence that the presence of glomerulations affects treatment outcomes.

In addition to traditional IC therapies, diet modification remains a core self care strategy as foods that are irritating to the bladder dramatically worsen the symptoms that people may experience. Foods high in acid and/or caffeine (such as all coffees, regular teas, green teas, sodas, diet sodas, artificial sweeteners and most fruit juices) should be avoided. [29] The daily goal should be to soothe rather than irritate the bladder wall. [28]

Related Research Articles

<span class="mw-page-title-main">Interstitial cystitis</span> Medical condition

Interstitial cystitis (IC), a type of bladder pain syndrome (BPS), is chronic pain in the bladder and pelvic floor of unknown cause. It is the urologic chronic pelvic pain syndrome of women. Symptoms include feeling the need to urinate right away, needing to urinate often, and pain with sex. IC/BPS is associated with depression and lower quality of life. Many of those affected also have irritable bowel syndrome and fibromyalgia.

<span class="mw-page-title-main">Urology</span> Medical specialty

Urology, also known as genitourinary surgery, is the branch of medicine that focuses on surgical and medical diseases of the urinary-tract system and the reproductive organs. Organs under the domain of urology include the kidneys, adrenal glands, ureters, urinary bladder, urethra, and the male reproductive organs.

<span class="mw-page-title-main">Urinary tract infection</span> Infection that affects part of the urinary tract

A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney infection (pyelonephritis). Symptoms from a lower urinary tract infection include pain with urination, frequent urination, and feeling the need to urinate despite having an empty bladder. Symptoms of a kidney infection include fever and flank pain usually in addition to the symptoms of a lower UTI. Rarely the urine may appear bloody. In the very old and the very young, symptoms may be vague or non-specific.

<span class="mw-page-title-main">Benign prostatic hyperplasia</span> Noncancerous increase in size of the prostate gland

Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss of bladder control. Complications can include urinary tract infections, bladder stones, and chronic kidney problems.

<span class="mw-page-title-main">Cystoscopy</span> Medical procedure; endoscopy of the urinary bladder via the urethra

Cystoscopy is endoscopy of the urinary bladder via the urethra. It is carried out with a cystoscope.

Dyspareunia is painful sexual intercourse due to medical or psychological causes. The term dyspareunia covers both female dyspareunia and male dyspareunia, but many discussions that use the term without further specification concern the female type, which is more common than the male type. In females, the pain can primarily be on the external surface of the genitalia, or deeper in the pelvis upon deep pressure against the cervix. Medically, dyspareunia is a pelvic floor dysfunction and is frequently underdiagnosed. It can affect a small portion of the vulva or vagina or be felt all over the surface. Understanding the duration, location, and nature of the pain is important in identifying the causes of the pain.

<span class="mw-page-title-main">Hematuria</span> Medical condition

Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. "Gross hematuria" occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable with a microscope or laboratory test. Blood that enters and mixes with the urine can come from any location within the urinary system, including the kidney, ureter, urinary bladder, urethra, and in men, the prostate. Common causes of hematuria include urinary tract infection (UTI), kidney stones, viral illness, trauma, bladder cancer, and exercise. These causes are grouped into glomerular and non-glomerular causes, depending on the involvement of the glomerulus of the kidney. But not all red urine is hematuria. Other substances such as certain medications and foods can cause urine to appear red. Menstruation in women may also cause the appearance of hematuria and may result in a positive urine dipstick test for hematuria. A urine dipstick test may also give an incorrect positive result for hematuria if there are other substances in the urine such as myoglobin, a protein excreted into urine during rhabdomyolysis. A positive urine dipstick test should be confirmed with microscopy, where hematuria is defined by three or more red blood cells per high power field. When hematuria is detected, a thorough history and physical examination with appropriate further evaluation can help determine the underlying cause.

<span class="mw-page-title-main">Urinary retention</span> Inability to completely empty the bladder

Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladder control, mild lower abdominal pain, and a weak urine stream. Those with long-term problems are at risk of urinary tract infections.

<span class="mw-page-title-main">Transitional epithelium</span> A type of tissue

Transitional epithelium is a type of stratified epithelium. Transitional epithelium is a type of tissue that changes shape in response to stretching. The transitional epithelium usually appears cuboidal when relaxed and squamous when stretched. This tissue consists of multiple layers of epithelial cells which can contract and expand in order to adapt to the degree of distension needed. Transitional epithelium lines the organs of the urinary system and is known here as urothelium. The bladder, for example, has a need for great distension.

Nocturia is defined by the International Continence Society (ICS) as “the complaint that the individual has to wake at night one or more times for voiding .” The term is derived from Latin nox, night, and Greek [τα] ούρα, urine. Causes are varied and can be difficult to discern. Although not every patient needs treatment, most people seek treatment for severe nocturia, waking up to void more than 2–3 times per night.

<span class="mw-page-title-main">Overactive bladder</span> Condition where a person has a frequent need to urinate

Overactive bladder (OAB) is a common condition where there is a frequent feeling of needing to urinate to a degree that it negatively affects a person's life. The frequent need to urinate may occur during the day, at night, or both. Loss of bladder control may occur with this condition. Overactive bladder affects approximately 11% of the population and more than 40% of people with overactive bladder have incontinence. Conversely, about 40% to 70% of urinary incontinence is due to overactive bladder. Overactive bladder is not life-threatening, but most people with the condition have problems for years.

<span class="mw-page-title-main">Urachal cancer</span> Medical condition

Urachal cancer is a very rare type of cancer arising from the urachus or its remnants. The disease might arise from metaplastic glandular epithelium or embryonic epithelial remnants originating from the cloaca region.

Lower urinary tract symptoms (LUTS) refer to a group of clinical symptoms involving the bladder, urinary sphincter, urethra and, in men, the prostate. The term is more commonly applied to men—over 40% of older men are affected—but lower urinary tract symptoms also affect women. The condition is also termed prostatism in men, but LUTS is preferred.

<span class="mw-page-title-main">Chronic prostatitis/chronic pelvic pain syndrome</span> Medical condition

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), previously known as chronic nonbacterial prostatitis, is long-term pelvic pain and lower urinary tract symptoms (LUTS) without evidence of a bacterial infection. It affects about 2–6% of men. Together with IC/BPS, it makes up urologic chronic pelvic pain syndrome (UCPPS).

Urinary bladder disease includes urinary bladder inflammation such as cystitis, bladder rupture and bladder obstruction (tamponade). Cystitis is common, sometimes referred to as urinary tract infection (UTI) caused by bacteria, bladder rupture occurs when the bladder is overfilled and not emptied while bladder tamponade is a result of blood clot formation near the bladder outlet.

Urologic diseases or conditions include urinary tract infections, kidney stones, bladder control problems, and prostate problems, among others. Some urologic conditions do not affect a person for that long and some are lifetime conditions. Kidney diseases are normally investigated and treated by nephrologists, while the specialty of urology deals with problems in the other organs. Gynecologists may deal with problems of incontinence in women.

<span class="mw-page-title-main">Eosinophilic cystitis</span> Medical condition

Eosinophilic cystitis is a rare type of interstitial cystitis first reported in 1960 by Edwin Brown. Eosinophilic cystitis has been linked to a number of etiological factors, including allergies, bladder tumors, trauma to the bladder, parasitic infections, and chemotherapy drugs, though the exact cause of the condition is still unknown. The antigen-antibody response is most likely the cause of eosinophilic cystitis. This results in the generation of different immunoglobulins, which activate eosinophils and start the inflammatory process.

<span class="mw-page-title-main">Emphysematous cystitis</span> Medical condition

Emphysematous cystitis is a rare type of infection of the bladder wall by gas-forming bacteria or fungi. The most frequent offending organism is E. coli. Other gram negative bacteria, including Klebsiella and Proteus are also commonly isolated. Fungi, such as Candida, have also been reported as causative organisms. Citrobacter and Enterococci have also been found to cause emphysematous cystitis. Although it is a rare type of bladder infection, it is the most common type of all gas-forming bladder infections. The condition is characterized by the formation of air bubbles in and around the bladder wall. The gas found in the bladder consists of nitrogen, hydrogen, oxygen, and carbon dioxide. The disease most commonly affects elderly diabetic and immunocompromised patients. The first case was identified in a post-mortem examination in 1888.

Urologic chronic pelvic pain syndrome (UCPPS) is ongoing bladder pain in either sex, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men and interstitial cystitis or painful bladder syndrome (IC/PBS) in women.

References

  1. ↑ Schmidt, Robert F.; Willis, William D., eds. (2007), "Glomerulations", Encyclopedia of Pain, Berlin, Heidelberg: Springer, p. 828, doi:10.1007/978-3-540-29805-2_1641, ISBN   978-3-540-29805-2 , retrieved 2021-07-30
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  3. 1 2 3 4 5 6 Ueda, Tomohiro; Hanno, Philip M.; Saito, Ryoichi; Meijlink, Jane M.; Yoshimura, Naoki (2021). "Current Understanding and Future Perspectives of Interstitial Cystitis/Bladder Pain Syndrome". International Neurourology Journal. 25 (2): 99–110. doi:10.5213/inj.2142084.042. ISSN   2093-4777. PMC   8255826 . PMID   34218637.
  4. 1 2 3 4 5 6 7 Wennevik, Gjertrud E.; Meijlink, Jane M.; Hanno, Philip; Nordling, Jørgen (2016). "The Role of Glomerulations in Bladder Pain Syndrome: A Review". The Journal of Urology. 195 (1): 19–25. doi:10.1016/j.juro.2015.06.112. ISSN   1527-3792. PMID   26318984.
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  18. ↑ Kiuchi, Hiroshi; Tsujimura, Akira; Takao, Tetsuya; Yamamoto, Keisuke; Nakayama, Jiro; Miyagawa, Yasushi; Nonomura, Norio; Takeyama, Masami; Okuyama, Akihiko (2009). "Increased vascular endothelial growth factor expression in patients with bladder pain syndrome/interstitial cystitis: its association with pain severity and glomerulations". BJU International. 104 (6): 826–831, discussion 831. doi: 10.1111/j.1464-410X.2009.08467.x . ISSN   1464-410X. PMID   19298410.
  19. ↑ Lee, Jane-Dar; Lee, Ming-Huei (2011). "Increased expression of hypoxia-inducible factor-1α and vascular endothelial growth factor associated with glomerulation formation in patients with interstitial cystitis". Urology. 78 (4): 971.e11–15. doi:10.1016/j.urology.2011.05.050. ISSN   1527-9995. PMID   21813166.
  20. ↑ van de Merwe, Joop P.; Nordling, Jørgen; Bouchelouche, Pierre; Bouchelouche, Kirsten; Cervigni, Mauro; Daha, L. Kurosch; Elneil, Suzy; Fall, Magnus; Hohlbrugger, Gero; Irwin, Paul; Mortensen, Svend (2008). "Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal". European Urology. 53 (1): 60–67. doi:10.1016/j.eururo.2007.09.019. ISSN   0302-2838. PMID   17900797.
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  22. 1 2 Loffroy, R.; Pottecher, P.; Cherblanc, V.; Favelier, S.; Estivalet, L.; Koutlidis, N.; Moulin, M.; Cercueil, J. P.; Cormier, L.; Krausé, D. (2014). "Current role of transcatheter arterial embolization for bladder and prostate hemorrhage". Diagnostic and Interventional Imaging. 95 (11): 1027–1034. doi: 10.1016/j.diii.2014.03.008 . ISSN   2211-5684. PMID   24746761.
  23. 1 2 "Bladder Bleeding - an overview | ScienceDirect Topics". www.sciencedirect.com. 2012.
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  26. ↑ Ali, Asad; Ali, Nouman Safdar; Malik, Muhammad Bilal; Sayyed, Zohaib; Ahmad, Malik Qistas (2018). "An Overview of the Pathology and Emerging Treatment Approaches for Interstitial Cystitis/Bladder Pain Syndrome". Cureus. 10 (9): e3321. doi: 10.7759/cureus.3321 . ISSN   2168-8184. PMC   6248749 . PMID   30473954.
  27. 1 2 "Intertitial Cystitis (IC/BPS) Guideline - American Urological Association". www.auanet.org. Retrieved 2021-07-29.
  28. 1 2 Cox, Ashley; Golda, Nicole; Nadeau, Genevieve; Curtis Nickel, J.; Carr, Lesley; Corcos, Jacques; Teichman, Joel (2016). "CUA guideline: Diagnosis and treatment of interstitial cystitis/bladder pain syndrome". Canadian Urological Association Journal. 10 (5–6): E136–E155. doi:10.5489/cuaj.3786. ISSN   1911-6470. PMC   5065402 . PMID   27790294.
  29. ↑ Waldman, Steven D. (2018). Atlas of Common Pain Syndromes E-Book. Elsevier Health Sciences. ISBN   978-0-323-54732-1.
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