Materiały źródłowe

• #1 Interstitial Cystitis/Bladder Pain Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK570588/

  Interstitial cystitis/bladder pain syndrome is a complex and chronic medical condition that primarily affects the urinary bladder, leading to a range of distressing symptoms. This disorder is characterized by the inflammation of the bladder’s lining, resulting in recurring and often severe discomfort, urgency, and frequency of urination. […] The etiology of IC/BPS is not well understood, and the current thoughts around its pathogenesis remain multifactorial. Current research strongly suggests an underlying inflammatory process, although the precise cause for this is not well-understood. […] Leading concepts regarding the underlying etiology of IC/BPS include the following: Autoimmune or immune-mediated processes, Chronic inflammation, Chronic stress, Fibrosis, Heightened pain sensitivity due to an increase in grey matter volume, Mast cell dysfunction or hyperactivation, Neurogenic inflammation/edema, Pelvic floor hypertonicity or dysfunction, Upregulation and proliferation of sensory afferent fibers, Urothelial dysfunction and exposure, especially in the epithelial and glycosaminoglycans (GAGs) layer, Vascular malformations that are seen as glomerulations on cystoscopy.

• #2 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Interstitial cystitis (IC) is a bladder syndrome of unknown etiology. The cause of IC is most likely multifactorial and includes genetic and environmental factors. […] The pathogenesis and etiology of interstitial cystitis remain incompletely defined. However, there is an emerging consensus as to the central role of epithelial dysfunction, bladder sensory nerve up-regulation, and mast cell activation in the genesis of IC. […] A sizable number of IC patients relate the onset of their symptoms to episodes of bacterial cystitis. […] Urinary antiproliferative factor (APF), recently described in IC, inhibits cell proliferation and impairs repair of damaged or denuded urothelium with resulting changes in the barrier function of the urothelium. […] IC has many features of an autoimmune diseasechronicity, exacerbations and remissions, clinical response to steroids/immunosuppressives, the high prevalence of antinuclear antibodies, and association with other autoimmune syndromes. Current evidence suggests that autoimmune phenomena (bladder antibodies, etc) are epi-phenomena that occur as a result of local bladder cellular damage.

• #3 Causes | Interstitial Cystitis Association

  https://www.ichelp.org/understanding-ic/learn-about-ic/causes/

  The exact cause of IC/BPS remains a mystery. […] The exact cause of interstitial cystitis/bladder pain syndrome (IC/BPS) remains a mystery, but researchers have identified a number of different factors that may contribute to the development of the condition. […] Many researchers believe a trigger (caused by one more events) may initially damage the bladder or bladder lining, and ultimately lead to the development of IC/BPS. […] Some of these triggers may be: Bladder trauma (such as from pelvic surgery), Bladder overdistention (anecdotal cases suggest onset after long periods without access to bathroom facilities), Pelvic floor muscle dysfunction, Autoimmune disorder, Bacterial infection (cystitis), Primary neurogenic inflammation (hypersensitivity or inflammation of pelvic nerves), Spinal cord trauma.

• #4 Interstitial cystitis – Wikipedia

  https://en.wikipedia.org/wiki/Interstitial_cystitis

  Interstitial cystitis (IC), a type of bladder pain syndrome (BPS), is chronic pain in the bladder and pelvic floor of unknown cause. […] The cause of interstitial cystitis is unknown. […] Several explanations have been proposed and include the following: 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 including exposure to abuse in childhood or adulthood. […] Regardless of the origin, most people with IC/BPS struggle with a damaged urothelium, or bladder lining. […] Most literature supports the belief that IC’s symptoms are associated with a defect in the bladder epithelium lining, allowing irritating substances in the urine to penetrate into the bladder.

• #5 Interstitial Cystitis(IC)/Bladder Pain Syndrome | University of Michigan Health

  https://www.uofmhealth.org/conditions-treatments/adult-urology/interstitial-cystitisic-bladder-pain-syndrome

  Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic bladder health issue. […] Experts do not know exactly what causes IC/BPS, but there are many theories, such as: […] A defect in the bladder tissue, which may allow irritating substances in the urine to penetrate the bladder. […] A specific type of inflammatory cell, called a mast cell. This cell releases histamine and other chemicals that lead to IC/BPS symptoms. […] Something in the urine that damages the bladder. […] Changes in the nerves that carry bladder sensations so pain is caused by events that are not normally painful (such as bladder filling). […] The body’s immune system attacks the bladder. This is similar to other autoimmune conditions. […] Having a family member with IC/BPS may increase your risk of getting IC/BPS. […] Patients with IC/BPS may have a substance in the urine that inhibits the growth of cells in the bladder tissue. So, some people may be more likely to get IC/BPS after an injury to the bladder, such as an infection.

• #6 Interstitial Cystitis/Bladder Pain Syndrome | IntechOpen

  https://www.intechopen.com/chapters/87191

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous, chronic, and debilitating condition. The exact etiology is not clearly understood. […] The etiology of IC/BPS is not fully understood. Some of the proposed theories are mentioned below. However, none of these theories has been proven. […] Good concordance of IC/BPS in monozygotic twins suggests genetic vulnerability. […] Urinary tract infection- bacterial or viral infection in the bladder induces an inflammatory process which continues even after clearing the infection. […] Leaky Glycosaminoglycan (GAG) layer- bladder urothelium is covered by glycosaminoglycans (GAG) which act as a protective lining against bacteria and irritants in the urine. It is hypothesized that disruption of the GAG layer results in increased permeability.

• #7 Interstitial Cystitis/Painful Bladder Syndrome – The Center for Specialized Women’s Health – Denville, NJ

  https://specializedwomenshealth.com/services/interstitial-cystitis-painful-bladder-syndrome/

  Interstitial cystitis (IC) is a term used to describe the condition of bladder pain or discomfort with a frequent and urgent need to pass urine. […] While we don’t currently know the causes of interstitial cystitis, we do know that it is not caused by bacterial or viral infections. Possible causes include a defect in the protective lining of the bladder wall, increased release of histamines, an increased number of nerve cells, and an autoimmune process (when antibodies are made that act against a part of the body) to name a few. […] In about 70% of people with interstitial cystitis, the protective layer lining the bladder is “leaky.” This may let urine irritate the bladder wall, causing interstitial cystitis. […] An inflammatory process may increase the release of histamines which result in interstitial cystitis symptoms. There may also be an increased number of nerve cells in the bladder wall which would increase sensitivity.

• #8 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Interstitial cystitis (IC) is a bladder syndrome of unknown etiology. The cause of IC is most likely multifactorial and includes genetic and environmental factors. […] The pathogenesis and etiology of interstitial cystitis remain incompletely defined. However, there is an emerging consensus as to the central role of epithelial dysfunction, bladder sensory nerve up-regulation, and mast cell activation in the genesis of IC. […] A sizable number of IC patients relate the onset of their symptoms to episodes of bacterial cystitis. […] Urinary antiproliferative factor (APF), recently described in IC, inhibits cell proliferation and impairs repair of damaged or denuded urothelium with resulting changes in the barrier function of the urothelium. […] IC has many features of an autoimmune diseasechronicity, exacerbations and remissions, clinical response to steroids/immunosuppressives, the high prevalence of antinuclear antibodies, and association with other autoimmune syndromes. Current evidence suggests that autoimmune phenomena (bladder antibodies, etc) are epi-phenomena that occur as a result of local bladder cellular damage.

• #9 Interstitial Cystitis – Painful Bladder Syndrome | Cooper University Health Care

  https://www.cooperhealth.org/services/interstitial-cystitis-painful-bladder-syndrome

  Many scientists believe that a trigger, such as one or more of these factors, may damage the bladder or its lining. This damage allows particles in the urine to leak into the lining, leading to further damage to the bladder and causing chronic pain. […] Research shows that this might be because of a protein called APF (antiproliferative factor) that is produced by the cells of people with IC (but not in healthy people).

• #10 Interstitial Cystitis/Bladder Pain Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK570588/

  Interstitial cystitis/bladder pain syndrome is a complex and chronic medical condition that primarily affects the urinary bladder, leading to a range of distressing symptoms. This disorder is characterized by the inflammation of the bladder’s lining, resulting in recurring and often severe discomfort, urgency, and frequency of urination. […] The etiology of IC/BPS is not well understood, and the current thoughts around its pathogenesis remain multifactorial. Current research strongly suggests an underlying inflammatory process, although the precise cause for this is not well-understood. […] Leading concepts regarding the underlying etiology of IC/BPS include the following: Autoimmune or immune-mediated processes, Chronic inflammation, Chronic stress, Fibrosis, Heightened pain sensitivity due to an increase in grey matter volume, Mast cell dysfunction or hyperactivation, Neurogenic inflammation/edema, Pelvic floor hypertonicity or dysfunction, Upregulation and proliferation of sensory afferent fibers, Urothelial dysfunction and exposure, especially in the epithelial and glycosaminoglycans (GAGs) layer, Vascular malformations that are seen as glomerulations on cystoscopy.

• #11 Interstitial Cystitis/Painful Bladder – Brigham and Women’s Hospital

  https://www.brighamandwomens.org/surgery/urology/interstitial-cystitis-painful-bladder

  The exact cause of IC is still unknown. Researchers are investigating theories to understand the causes of IC and to determine appropriate treatments. These include: […] Defect in the bladder epithelium that allows irritating urine substances to penetrate the bladder […] Inflammatory cells releasing histamine and other chemicals […] Something in the urine that damages the bladder […] Change in nerves that carry bladder sensations […] Body’s immune system attacks the bladder […] Substance in urine inhibits the growth of cells in the bladder epithelium […] Certain foods worsen symptoms, including citrus fruits, tomatoes, chocolate, coffee, and potassium-rich foods.

• #12 Interstitial Cystitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/2055505-overview

  Interstitial cystitis is a clinical syndrome characterized by daytime and nighttime urinary frequency, urgency, and pelvic pain. Interstitial cystitis has no clear etiology or pathophysiology, and diagnostic criteria for the syndrome remain undefined. […] The etiology of interstitial cystitis remains unknown and is likely multifactorial. Proposed etiologies include the following: pathogenic role of mast cells in the detrusor and/or mucosal layers of the bladder; deficiency in the glycosaminoglycan layer on the luminal surface of the bladder, resulting in increased permeability of the underlying submucosal tissues to toxic substances in the urine; infection with a poorly characterized agent (eg, a slow-growing virus or an extremely fastidious bacterium); production of a toxic substance in the urine; neurogenic hypersensitivity or inflammation mediated locally at the bladder or spinal cord level; manifestation of pelvic floor muscle dysfunction or dysfunctional voiding; autoimmune disorder.

• #13 Interstitial cystitis – Wikipedia

  https://en.wikipedia.org/wiki/Interstitial_cystitis

  Deficiency in this glycosaminoglycan layer on the surface of the bladder results in increased permeability of the underlying submucosal tissues. […] Numerous studies have noted the link between IC, anxiety, stress, hyper-responsiveness, panic, and abuse. […] Another proposed mechanism for interstitial cystitis is the autoimmune mechanism. […] Biopsies on the bladder walls of people with IC may contain mast cells. […] Additionally, another proposed mechanism is increased activity of unspecified nerves in the bladder wall.

• #14 Interstitial Cystitis/Bladder Pain Syndrome | IntechOpen

  https://www.intechopen.com/chapters/87191

  Autoimmune reaction- autoimmunity may sometimes be responsible for IC/BPS. […] Hypersensitivity reaction- In some cases, mast cell proliferation in the bladder wall biopsies is observed. […] A functional brain magnetic resonance imaging (MRI) study of patients with IC/BPS revealed an increase in the gray matter volume in brain areas related to pain, highlighting the role of the nervous system in the disease. […] Neurologic upregulation- some experts believe that recurrent bladder wall inflammation or irritation results in hyperplasia of the sensory nerves, enhancing pain perception. […] Recreational use of ketamine is associated with severe IC/BPS. Possible explanations include autoimmunity, infection, urothelial damage, and vascular changes due to ketamine or metabolites.

• #15 Interstitial Cystitis/Bladder Pain Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK570588/

  The underlying pathophysiology of IC/BPS is somewhat uncertain, contributing to the lack of a definitive, curative remedy. Known involved bladder pathological findings include chronic inflammation, afferent sensory hyperactivity, nociceptor upregulation, mast cell overactivity, submucosal microvascular abnormalities, autoimmune disorders, lack of normal bladder epithelial cell growth, and urothelial thinning with a deficient or dysfunctional superficial mucosal GAGs layer. […] Chronic stress is found in 50% of IC/BPS patients, which is a factor in the development and exacerbation of symptoms. […] The chronic pain typically associated with IC/BPS is caused by sensory afferent nerve activity and central nervous system sensitization.

• #16 Interstitial Cystitis/Bladder Pain Syndrome | IntechOpen

  https://www.intechopen.com/chapters/87191

  Autoimmune reaction- autoimmunity may sometimes be responsible for IC/BPS. […] Hypersensitivity reaction- In some cases, mast cell proliferation in the bladder wall biopsies is observed. […] A functional brain magnetic resonance imaging (MRI) study of patients with IC/BPS revealed an increase in the gray matter volume in brain areas related to pain, highlighting the role of the nervous system in the disease. […] Neurologic upregulation- some experts believe that recurrent bladder wall inflammation or irritation results in hyperplasia of the sensory nerves, enhancing pain perception. […] Recreational use of ketamine is associated with severe IC/BPS. Possible explanations include autoimmunity, infection, urothelial damage, and vascular changes due to ketamine or metabolites.

• #17 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Interstitial-Cystitis-Causes.aspx

  Although a genetic link is unlikely to be the sole cause of interstitial cystitis, it may be possible for individuals to inherit a predisposition to the condition. […] In some patients, there may be damage to the nerves that are responsible for carrying sensory messages from the bladder. This has the potential to cause the pain associated with normal physiological events, such as the filling of the bladder. […] An autoimmune response involving the destruction of the cells in the bladder has also been proposed as a cause of the condition. It is more common for individuals with an autoimmune disorder to suffer from interstitial cystitis, which suggests autoimmunity may be involved in the pathophysiology. […] Interstitial cystitis has been linked to several other conditions, due to the high frequency of patients that present concurrently with other symptoms and conditions.

• #18 Interstitial Cystitis/Bladder Pain Syndrome | IntechOpen

  https://www.intechopen.com/chapters/87191

  Autoimmune reaction- autoimmunity may sometimes be responsible for IC/BPS. […] Hypersensitivity reaction- In some cases, mast cell proliferation in the bladder wall biopsies is observed. […] A functional brain magnetic resonance imaging (MRI) study of patients with IC/BPS revealed an increase in the gray matter volume in brain areas related to pain, highlighting the role of the nervous system in the disease. […] Neurologic upregulation- some experts believe that recurrent bladder wall inflammation or irritation results in hyperplasia of the sensory nerves, enhancing pain perception. […] Recreational use of ketamine is associated with severe IC/BPS. Possible explanations include autoimmunity, infection, urothelial damage, and vascular changes due to ketamine or metabolites.

• #19 Interstitial Cystitis/Bladder Pain Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK570588/

  Interstitial cystitis/bladder pain syndrome is a complex and chronic medical condition that primarily affects the urinary bladder, leading to a range of distressing symptoms. This disorder is characterized by the inflammation of the bladder’s lining, resulting in recurring and often severe discomfort, urgency, and frequency of urination. […] The etiology of IC/BPS is not well understood, and the current thoughts around its pathogenesis remain multifactorial. Current research strongly suggests an underlying inflammatory process, although the precise cause for this is not well-understood. […] Leading concepts regarding the underlying etiology of IC/BPS include the following: Autoimmune or immune-mediated processes, Chronic inflammation, Chronic stress, Fibrosis, Heightened pain sensitivity due to an increase in grey matter volume, Mast cell dysfunction or hyperactivation, Neurogenic inflammation/edema, Pelvic floor hypertonicity or dysfunction, Upregulation and proliferation of sensory afferent fibers, Urothelial dysfunction and exposure, especially in the epithelial and glycosaminoglycans (GAGs) layer, Vascular malformations that are seen as glomerulations on cystoscopy.

• #20 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Interstitial cystitis (IC) is a bladder syndrome of unknown etiology. The cause of IC is most likely multifactorial and includes genetic and environmental factors. […] The pathogenesis and etiology of interstitial cystitis remain incompletely defined. However, there is an emerging consensus as to the central role of epithelial dysfunction, bladder sensory nerve up-regulation, and mast cell activation in the genesis of IC. […] A sizable number of IC patients relate the onset of their symptoms to episodes of bacterial cystitis. […] Urinary antiproliferative factor (APF), recently described in IC, inhibits cell proliferation and impairs repair of damaged or denuded urothelium with resulting changes in the barrier function of the urothelium. […] IC has many features of an autoimmune diseasechronicity, exacerbations and remissions, clinical response to steroids/immunosuppressives, the high prevalence of antinuclear antibodies, and association with other autoimmune syndromes. Current evidence suggests that autoimmune phenomena (bladder antibodies, etc) are epi-phenomena that occur as a result of local bladder cellular damage.

• #21 Interstitial Cystitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/2055505-overview

  Although interstitial cystitis has not traditionally been considered a heritable condition, a 2005 study from the University of Maryland reported a higher occurrence of interstitial cystitis in monozygotic versus dizygotic twins, suggesting the disease has at least a partial genetic predisposition. […] Other autoimmune conditions have also been shown to bear resemblance or be associated with IC/BPS. Sjgren syndrome and fibromyalgia show antibodies against urothelium, smooth muscle, and connective-tissue components of the urinary bladder. Indeed, the pathophysiology of those conditions is similar to that of IC/BPS.

• #22 Bladder Pain Syndrome | GLOWM

  https://www.glowm.com/section-view/heading/Bladder%20Pain%20Syndrome/item/865

  An increased number of activated bladder mast cells has been reported repeatedly in BPS/IC. […] The protective inner layer of the bladder is made up of glycosaminoglycans (GAGs), chondroitin sulphate (CS), and sodium hyaluronate (SH). […] BPS/IC is not an end-organ condition; it should be considered a condition of the peripheral and central nervous systems as they relate to acute or chronic pain. […] A decrease in the microvascular density has been observed in the suburothelium in patients with BPS/IC. […] Many of the clinical features of BPS/IC reflect an autoimmune component of the disease process.

• #23 Interstitial Cystitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/2055505-overview

  Although interstitial cystitis has not traditionally been considered a heritable condition, a 2005 study from the University of Maryland reported a higher occurrence of interstitial cystitis in monozygotic versus dizygotic twins, suggesting the disease has at least a partial genetic predisposition. […] Other autoimmune conditions have also been shown to bear resemblance or be associated with IC/BPS. Sjgren syndrome and fibromyalgia show antibodies against urothelium, smooth muscle, and connective-tissue components of the urinary bladder. Indeed, the pathophysiology of those conditions is similar to that of IC/BPS.

• #24 What Causes Bladder Pain Without Infection?

  https://www.healthline.com/health/what-causes-bladder-pain-without-infection

  Bladder pain without an infection may be due to damage to your bladders lining, problems with your pelvic floor muscles, or inflammation. […] Conditions like bladder pain syndrome (BPS) and, in rare cases, bladder cancer can also cause similar symptoms. […] If youre experiencing bladder pain without an infection, you may have bladder pain syndrome (BPS), also known as painful bladder syndrome or interstitial cystitis. BPS can have different causes. […] Damage to the bladders lining may cause pee to irritate it. Damage to the bladder may also impact surrounding nerves, causing pain. […] One potential reason for bladder lining damage is surgical complications. Growths and cysts can also contribute to problems with the bladders lining. […] Weakened or dysfunctional pelvic floor muscles may reduce the control you have over your bladder and peeing.

• #25 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Interstitial cystitis (IC) is a bladder syndrome of unknown etiology. The cause of IC is most likely multifactorial and includes genetic and environmental factors. […] The pathogenesis and etiology of interstitial cystitis remain incompletely defined. However, there is an emerging consensus as to the central role of epithelial dysfunction, bladder sensory nerve up-regulation, and mast cell activation in the genesis of IC. […] A sizable number of IC patients relate the onset of their symptoms to episodes of bacterial cystitis. […] Urinary antiproliferative factor (APF), recently described in IC, inhibits cell proliferation and impairs repair of damaged or denuded urothelium with resulting changes in the barrier function of the urothelium. […] IC has many features of an autoimmune diseasechronicity, exacerbations and remissions, clinical response to steroids/immunosuppressives, the high prevalence of antinuclear antibodies, and association with other autoimmune syndromes. Current evidence suggests that autoimmune phenomena (bladder antibodies, etc) are epi-phenomena that occur as a result of local bladder cellular damage.

• #26 Interstitial Cystitis/Bladder Pain Syndrome | IntechOpen

  https://www.intechopen.com/chapters/87191

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous, chronic, and debilitating condition. The exact etiology is not clearly understood. […] The etiology of IC/BPS is not fully understood. Some of the proposed theories are mentioned below. However, none of these theories has been proven. […] Good concordance of IC/BPS in monozygotic twins suggests genetic vulnerability. […] Urinary tract infection- bacterial or viral infection in the bladder induces an inflammatory process which continues even after clearing the infection. […] Leaky Glycosaminoglycan (GAG) layer- bladder urothelium is covered by glycosaminoglycans (GAG) which act as a protective lining against bacteria and irritants in the urine. It is hypothesized that disruption of the GAG layer results in increased permeability.

• #27 Patient education: Diagnosis of interstitial cystitis/bladder pain syndrome (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/diagnosis-of-interstitial-cystitis-bladder-pain-syndrome-beyond-the-basics/print

  One or more events may lead to the symptoms of IC/BPS, including: Urinary tract infection, An episode of vaginitis or prostatitis (eg, an infection of the vagina or a bacterial infection of the prostate), Bladder, pelvic, back, or other type of surgery, Trauma (eg, fall onto the tailbone [coccyx] or car accident). […] However, in many people, there is no clear explanation for why or how the symptoms of IC/BPS first began.

• #28 Bladder pain syndrome (interstitial cystitis)

  https://www.nhs.uk/conditions/interstitial-cystitis/

  Bladder pain syndrome (BPS) is a poorly understood condition where you have pelvic pain and problems peeing. […] The exact cause of BPS (interstitial cystitis) is not clear. However, there are several ideas about what might cause it. […] These include: damage to the bladder lining, which may mean pee can irritate the bladder and surrounding nerves; a problem with the pelvic floor muscles used to control peeing; your immune system causing an inflammatory reaction. […] Some people who have been diagnosed with BPS (interstitial cystitis), may have a long-term (chronic) urinary infection (UTI) in the bladder, which has not been picked up by current urine tests. […] BPS (interstitial cystitis) may also be associated with chronic conditions such as fibromyalgia, myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) and irritable bowel syndrome (IBS).

• #29 Interstitial Cystitis/Painful Bladder Syndrome – The Urology Foundation

  https://www.theurologyfoundation.org/urology-health/bladder-conditions/5631-2/

  Interstitial cystitis (IC) is now also commonly referred to as a collection of symptoms known as painful bladder syndrome (PBS). […] Interstitial cystitis/painful bladder syndrome is a chronic condition that is characterised by varying degrees of bladder pain and discomfort. […] The exact cause is not known, but theories include a defect in the bladder lining, an abnormal immune response, or nerve sensitivity. […] Some experts think that an undetected longstanding infection that has been undetectable by standard testing might also contribute to IC/PBS. […] Some patients may exhibit signs of inflammation in the bladder, especially those with Hunner’s ulcers, but visible inflammation is not always present. […] Hunner’s ulcers are lesions found in the bladder walls of some IC/PBS patients and are found during a telescopic examination of the bladder (cystoscopy). […] Glomerulations are areas of pinpoint bleeding that can sometimes be observed during a cystoscopy in some people with IC/PBS.

• #30 Interstitial Cystitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/2055505-overview

  Interstitial cystitis is a clinical syndrome characterized by daytime and nighttime urinary frequency, urgency, and pelvic pain. Interstitial cystitis has no clear etiology or pathophysiology, and diagnostic criteria for the syndrome remain undefined. […] The etiology of interstitial cystitis remains unknown and is likely multifactorial. Proposed etiologies include the following: pathogenic role of mast cells in the detrusor and/or mucosal layers of the bladder; deficiency in the glycosaminoglycan layer on the luminal surface of the bladder, resulting in increased permeability of the underlying submucosal tissues to toxic substances in the urine; infection with a poorly characterized agent (eg, a slow-growing virus or an extremely fastidious bacterium); production of a toxic substance in the urine; neurogenic hypersensitivity or inflammation mediated locally at the bladder or spinal cord level; manifestation of pelvic floor muscle dysfunction or dysfunctional voiding; autoimmune disorder.

• #31 Understanding Painful Bladder Syndrome | Pelvic Pain Doc

  https://www.pelvicpaindoc.com/blog/understanding-painful-bladder-syndrome/

  Even though we don’t fully understand the exact cause of bladder pain syndrome, it has been associated with several risk factors, including: Other chronic pain syndromes: If you have a condition such as fibromyalgia, irritable bowel syndrome, or rheumatoid arthritis, you may have an increased risk of developing interstitial cystitis. Gender: Bladder pain syndrome is significantly more common in women than in men, although men can still have the condition. Skin and hair color: People with fair skin and red hair are more likely to have interstitial cystitis. Age: Most cases of interstitial cystitis are diagnosed in the patients 30s but are seen in patients as young as 12 and in patients over the age of 65.

• #32 Interstitial Cystitis and Chronic Pain Syndrome

  https://www.uspharmacist.com/article/interstitial-cystitis-and-chronic-pain-syndrome

  Interstitial cystitis (IC), also known as painful bladder syndrome (PBS), is more common than was previously thought; however, the disorder is difficult to diagnose and treat. […] IC/PBS is a chronic disease of unknown etiology; however, several theories exist, and the pathophysiology of IC/PBS is considered to be multifactorial. […] Although the underlying pathophysiology of IC/PBS is not completely understood, it is thought to involve changes in the bladder urothelium, mast-cell activation, and neurogenic inflammation. […] The only definitive risk factor for IC/PBS is female gender, with a female:male ratio of 10:1. […] IC/PBS is more common in women than in men. […] Some experts believe that IC/PBS may be a bladder manifestation of a more general condition, such as fibromyalgia or irritable bowel syndrome, that causes inflammation in various organs and areas of the body. […] IC/PBS is a chronic disease of unknown etiology that is often difficult to diagnose and treat.

• #33 Interstitial Cystitis – MidLantic Urology LLC

  https://midlanticurology.com/conditions/interstitial-cystitis/

  Far more common in women than men, interstitial cystitis causes bladder pressure, pain in the bladder and pelvic region, and sometimes pain with intercourse. […] The exact cause of interstitial cystitis isnt known, but its likely that there are many contributing factors. People with interstitial cystitis may have a defect in the protective lining (epithelium) of the bladder. A leak in the epithelium may allow toxic substances in urine to irritate the bladder wall. […] Other possible, but unproven, contributing factors are an autoimmune reaction, heredity, infection or allergy. […] Factors associated with a higher risk of interstitial cystitis are: Biological Sex: Women are 10 times more likely to be diagnosed with interstitial cystitis than men. Up to 12% of women are affected. Age: Most people with interstitial cystitis are diagnosed during their 30s or older. Having a chronic pain disorder: Interstitial cystitis may be associated with other chronic pain disorders, such as irritable bowel syndrome or fibromyalgia.

• #34 Advanced Gynecology – Painful Bladder Syndrome

  https://advancedgynecology.com/urogynecology-conditions/painful-bladder-syndrome

  An autoimmune reaction […] Heredity: sex, skin and hair color may put one at risk. Women with fair skin and red hair have been associated with greater risk of IC/PBS […] Age: most people with IC/PBS are diagnosed during their 30s or older […] Infection […] Allergy […] Having previously been diagnosed with another pain disorder such as irritable bowel syndrome or fibromyalgia.

• #35 Bladder pain syndrome (interstitial cystitis)

  https://www.nhs.uk/conditions/interstitial-cystitis/

  Bladder pain syndrome (BPS) is a poorly understood condition where you have pelvic pain and problems peeing. […] The exact cause of BPS (interstitial cystitis) is not clear. However, there are several ideas about what might cause it. […] These include: damage to the bladder lining, which may mean pee can irritate the bladder and surrounding nerves; a problem with the pelvic floor muscles used to control peeing; your immune system causing an inflammatory reaction. […] Some people who have been diagnosed with BPS (interstitial cystitis), may have a long-term (chronic) urinary infection (UTI) in the bladder, which has not been picked up by current urine tests. […] BPS (interstitial cystitis) may also be associated with chronic conditions such as fibromyalgia, myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) and irritable bowel syndrome (IBS).

• #36 What Causes Bladder Pain Without Infection?

  https://www.healthline.com/health/what-causes-bladder-pain-without-infection

  A chronic urinary tract infection can cause bladder inflammation, but an autoimmune condition may also cause it. […] Bladder inflammation and pain may also be related to chronic conditions such as: fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome (IBS). […] People with these conditions are at an increased risk for bladder pain. […] Your bladder may hurt because of damage to its lining, a problem with your pelvic floor muscles, or an inflammatory reaction not caused by an infection. […] Certain chronic conditions, such as fibromyalgia and irritable bowel syndrome (IBS), may also cause bladder pain. […] Bladder pain can be the result of damage to the bladders lining, problems with pelvic floor muscles, or inflammation from chronic conditions.

• #37 Interstitial Cystitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/2055505-overview

  Although interstitial cystitis has not traditionally been considered a heritable condition, a 2005 study from the University of Maryland reported a higher occurrence of interstitial cystitis in monozygotic versus dizygotic twins, suggesting the disease has at least a partial genetic predisposition. […] Other autoimmune conditions have also been shown to bear resemblance or be associated with IC/BPS. Sjgren syndrome and fibromyalgia show antibodies against urothelium, smooth muscle, and connective-tissue components of the urinary bladder. Indeed, the pathophysiology of those conditions is similar to that of IC/BPS.

• #38 Interstitial Cystitis: Causes, Symptoms, and Diagnosis

  https://www.healthline.com/health/interstitial-cystitis

  What causes IC? […] The exact cause of IC isnt known, but researchers postulate that several factors may damage the lining of the bladder and therefore trigger the disorder. These include: […] Many people with IC also have irritable bowel syndrome (IBS) or fibromyalgia. Some researchers believe that IC may be part of a generalized inflammatory disorder that affects multiple organ systems. […] Researchers are also investigating the possibility that people may inherit a genetic predisposition to IC. Although its not common, IC has been reported in blood relatives. Cases have been seen in mother and daughter as well as in two or more sisters. […] Research is ongoing to determine the cause of IC and to develop more effective treatments.

• #39 Interstitial Cystitis – Painful Bladder Syndrome | Cooper University Health Care

  https://www.cooperhealth.org/services/interstitial-cystitis-painful-bladder-syndrome

  Interstitial cystitis (IC), also called painful bladder syndrome, is a chronic condition in which the walls of the bladder are irritated and inflamed. […] The exact cause of IC isnt known, but some possible causes include bladder trauma, pelvic floor muscle dysfunction, bacterial bladder infection (cystitis), or autoimmune disorder. […] The specific cause of IC is still not clearly known, but scientists have pinpointed several factors that may contribute to developing this condition: Trauma to the bladder, such as from pelvic surgery, Pelvic floor muscle dysfunction, Bladder overdistention (stretching) if you repeatedly go long periods without urinating, Autoimmune disorder(s), Bacterial bladder infection (cystitis), Inflammation or hypersensitivity of the pelvic nerves (neurogenic inflammation), Damage to the spinal cord.

• #40 Causes of Interstitial Cystitis/Painful Bladder Syndrome

  https://pelvicpainrehab.com/blog/causes-of-interstitial-cystitis-painful-bladder-syndrome/

  Some people develop IC symptoms after a series of culture-proven UTIs, the symptoms can persist when the infection has cleared. […] The specific cause of Interstitial Cystitis is still not clearly known, but several factors have been identified that may contribute to developing this condition. One of these factors includes trauma to the bladder, such as from pelvic surgery or orthopedic injuries. There are many causes of IC/PBS, including: Orthopedic injuries/trauma, Surgical trauma, Endometriosis, GI dysregulation. […] Its important to consult with a healthcare provider if you suspect you may have Interstitial Cystitis or if you experience persistent bladder pain or discomfort, especially if these symptoms coincide with a history of bladder trauma or orthopedic injuries. […] We understand that IC is commonly seen in people with vulvodynia, endometriosis, and fibromyalgia. Understanding the underlying cause/causes is part of what we work to figure out during pelvic floor physical therapy. […] Research has shown the majority of patients who meet the clinical definition have pelvic floor dysfunction and myalgia. Therefore, the American Urologic Association recommends pelvic floor physical therapy as first-line treatment for Interstitial Cystitis.

• #41 Causes | Interstitial Cystitis Association

  https://www.ichelp.org/understanding-ic/learn-about-ic/causes/

  The exact cause of IC/BPS remains a mystery. […] The exact cause of interstitial cystitis/bladder pain syndrome (IC/BPS) remains a mystery, but researchers have identified a number of different factors that may contribute to the development of the condition. […] Many researchers believe a trigger (caused by one more events) may initially damage the bladder or bladder lining, and ultimately lead to the development of IC/BPS. […] Some of these triggers may be: Bladder trauma (such as from pelvic surgery), Bladder overdistention (anecdotal cases suggest onset after long periods without access to bathroom facilities), Pelvic floor muscle dysfunction, Autoimmune disorder, Bacterial infection (cystitis), Primary neurogenic inflammation (hypersensitivity or inflammation of pelvic nerves), Spinal cord trauma.

• #42 Causes | Interstitial Cystitis Association

  https://www.ichelp.org/understanding-ic/learn-about-ic/causes/

  The exact cause of IC/BPS remains a mystery. […] The exact cause of interstitial cystitis/bladder pain syndrome (IC/BPS) remains a mystery, but researchers have identified a number of different factors that may contribute to the development of the condition. […] Many researchers believe a trigger (caused by one more events) may initially damage the bladder or bladder lining, and ultimately lead to the development of IC/BPS. […] Some of these triggers may be: Bladder trauma (such as from pelvic surgery), Bladder overdistention (anecdotal cases suggest onset after long periods without access to bathroom facilities), Pelvic floor muscle dysfunction, Autoimmune disorder, Bacterial infection (cystitis), Primary neurogenic inflammation (hypersensitivity or inflammation of pelvic nerves), Spinal cord trauma.

• #43 Causes of Interstitial Cystitis/Painful Bladder Syndrome

  https://pelvicpainrehab.com/blog/causes-of-interstitial-cystitis-painful-bladder-syndrome/

  Interstitial Cystitis/ Painful Bladder Syndrome is a treatable pelvic pain syndrome affecting roughly 12 million people in the United States alone. If it affects so many, what are the causes? Were glad you asked! Theres many! […] Multiple studies conducted in the US and abroad show that up to 92% of people with IC/Painful Bladder Syndrome have pelvic floor dysfunction. The prevalence is so high that the American Urologic Association classified pelvic floor dysfunction as a phenotype, or subset, of IC in 2022. […] Others may develop symptoms in response to hormonal deficiencies, which can occur from using oral contraceptive birth control bills, certain prescription acne medications, while breastfeeding, or in perimenopause/menopause. […] Some people have central nervous system sensitivities and experience body-wide pain and the symptoms of IC. CNS is another subset, or phenotype of IC.

• #44 What Causes Bladder Pain Without Infection?

  https://www.healthline.com/health/what-causes-bladder-pain-without-infection

  Bladder pain without an infection may be due to damage to your bladders lining, problems with your pelvic floor muscles, or inflammation. […] Conditions like bladder pain syndrome (BPS) and, in rare cases, bladder cancer can also cause similar symptoms. […] If youre experiencing bladder pain without an infection, you may have bladder pain syndrome (BPS), also known as painful bladder syndrome or interstitial cystitis. BPS can have different causes. […] Damage to the bladders lining may cause pee to irritate it. Damage to the bladder may also impact surrounding nerves, causing pain. […] One potential reason for bladder lining damage is surgical complications. Growths and cysts can also contribute to problems with the bladders lining. […] Weakened or dysfunctional pelvic floor muscles may reduce the control you have over your bladder and peeing.

• #45 Interstitial Cystitis (IC): Causes, Diagnosis & Treatment

  https://atlanticurologyclinics.com/conditions/interstitial-cystitis/

  Some researchers propose that nerve growth factors are overproduced, leading to pain and inflammatory symptoms. […] Tension or dysfunction in the pelvic floor muscles may contribute to the development of IC. […] There is evidence to suggest that, for some individuals, interstitial cystitis may be an autoimmune disorder. […] Some research indicates a potential genetic component, as the condition seems to occur more in individuals with a family history of the syndrome.

• #46 Interstitial Cystitis (Painful Bladder Syndrome) | Enid Urology Associates

  https://www.enidurologyassociates.com/services-and-procedures/interstitial-cystitis

  Interstitial cystitis (IC) is a condition that results in recurring discomfort or pain in the bladder and the surrounding pelvic region. […] Because IC varies so much in symptoms and severity, most researchers believe it is not one, but several diseases. […] The term IC/PBS includes all cases of urinary pain that cant be attributed to other causes, such as infection or urinary stones. […] Many different problems can cause urgency, frequency, and bladder pain. Just a few of them are: infections, bowel disorders, endometriosis, bladder cancer. […] Sometimes the cause is hard to find. If all the test results are normal and all other diseases are ruled out, your doctor may find that you have IC/PBS. […] People with IC/PBS rarely have bladder pain all the time. […] Stress may bring on a flare-up of symptoms in someone who has IC/PBS. But stress does not cause a person to get IC/PBS.

• #47 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  No single pathological process is universally present in IC. IC may well have multiple etiologies that result in the symptoms of irritative voiding and pain. […] The multifactorial etiology of IC and its complex, interrelated pathogenesis involving the bladder urothelium, sensory nerves, and mast cells are being increasingly defined.

• #48 The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/12/9/2051

  The initial bladder insult may trigger an inflammatory cascade that causes local and central inflammation and the subsequent manifestation of clinical symptoms. […] Chronic inflammation of the bladder wall is the fundamental pathophysiology of IC/BPS. […] Chronic inflammation in IC/BPS may be induced by toxins, bacterial infection, surgical trauma, autoimmune reactions, or systemic disorders. […] The pathophysiology of IC/BPS includes chronic inflammation, viral infection, urothelial dysfunction, sensory nerve hyperplasia, lymphoplasmatic cell infiltration, chronic lymphoid follicle aggregation, bladder wall thickening, central nervous system sensitization, extravesical inflammation, and psychological stress.

• #49 The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/12/9/2051

  The initial bladder insult may trigger an inflammatory cascade that causes local and central inflammation and the subsequent manifestation of clinical symptoms. […] Chronic inflammation of the bladder wall is the fundamental pathophysiology of IC/BPS. […] Chronic inflammation in IC/BPS may be induced by toxins, bacterial infection, surgical trauma, autoimmune reactions, or systemic disorders. […] The pathophysiology of IC/BPS includes chronic inflammation, viral infection, urothelial dysfunction, sensory nerve hyperplasia, lymphoplasmatic cell infiltration, chronic lymphoid follicle aggregation, bladder wall thickening, central nervous system sensitization, extravesical inflammation, and psychological stress.

• #50 The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/12/9/2051

  The initial bladder insult may trigger an inflammatory cascade that causes local and central inflammation and the subsequent manifestation of clinical symptoms. […] Chronic inflammation of the bladder wall is the fundamental pathophysiology of IC/BPS. […] Chronic inflammation in IC/BPS may be induced by toxins, bacterial infection, surgical trauma, autoimmune reactions, or systemic disorders. […] The pathophysiology of IC/BPS includes chronic inflammation, viral infection, urothelial dysfunction, sensory nerve hyperplasia, lymphoplasmatic cell infiltration, chronic lymphoid follicle aggregation, bladder wall thickening, central nervous system sensitization, extravesical inflammation, and psychological stress.

• #51 Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/interstitial-cystitis-bladder-pain-syndrome-clinical-features-and-diagnosis

  Chronic bladder pain can be a debilitating condition that impacts quality of life. The pathophysiology of chronic bladder pain is not well understood, and symptoms likely represent more than one underlying etiology. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a diagnosis that applies to patients with chronic bladder pain in the absence of other explanatory etiologies. […] Chronic bladder pain in the absence of an identifiable etiology has historically been called interstitial cystitis. This term is a misnomer, however, since there is no clear evidence that bladder inflammation (cystitis) is involved in the etiology or pathophysiology of the condition, nor is there evidence that the condition is reliably associated with abnormalities of the interstitium of the bladder. […] The understanding is that patients with these symptoms have a chronic pain condition of the bladder, analogous to other poorly understood chronic pain conditions such as fibromyalgia or irritable bowel syndrome.

• #52 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  No single pathological process is universally present in IC. IC may well have multiple etiologies that result in the symptoms of irritative voiding and pain. […] The multifactorial etiology of IC and its complex, interrelated pathogenesis involving the bladder urothelium, sensory nerves, and mast cells are being increasingly defined.

• #53 Interstitial Cystitis and Chronic Pain Syndrome

  https://www.uspharmacist.com/article/interstitial-cystitis-and-chronic-pain-syndrome

  Interstitial cystitis (IC), also known as painful bladder syndrome (PBS), is more common than was previously thought; however, the disorder is difficult to diagnose and treat. […] IC/PBS is a chronic disease of unknown etiology; however, several theories exist, and the pathophysiology of IC/PBS is considered to be multifactorial. […] Although the underlying pathophysiology of IC/PBS is not completely understood, it is thought to involve changes in the bladder urothelium, mast-cell activation, and neurogenic inflammation. […] The only definitive risk factor for IC/PBS is female gender, with a female:male ratio of 10:1. […] IC/PBS is more common in women than in men. […] Some experts believe that IC/PBS may be a bladder manifestation of a more general condition, such as fibromyalgia or irritable bowel syndrome, that causes inflammation in various organs and areas of the body. […] IC/PBS is a chronic disease of unknown etiology that is often difficult to diagnose and treat.

• #54 The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/12/9/2051

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. […] Hunner’s (HIC) and non-Hunner’s IC (NHIC), each with distinct clinical presentations, urothelial dysfunction, chronic inflammation, and central sensitization and thus multimodal symptomatic treatment approaches, may be the most common pathogeneses of IC/BPS. […] Several possible pathogeneses of IC/BPS have been proposed based on patients’ medical history, histopathological bladder findings, urinary biomarker analysis, and immunohistochemical studies. Various conditions may contribute to the development of IC/BPS, including autoimmune reactions after acute bacterial cystitis; mast cell activation due to toxins, stress, or allergies; urothelial dysfunction after bladder wall injury; neurogenic activation through the upregulated release of sensory fibers by neuropeptides; and central sensitization.

• #55 Interstitial cystitis / bladder pain syndrome – Symptoms, Causes, Images, and Treatment Options

  https://www.epocrates.com/online/diseases/297/interstitial-cystitis-bladder-pain-syndrome

  Interstitial cystitis (bladder pain syndrome) is a chronic, often debilitating clinical syndrome of urinary frequency, urgency, and pelvic pain. Symptoms vary with bladder filling. […] Diagnosis is one of exclusion, and physicians must carefully consider all patients with chronic pelvic pain as potential candidates. […] Associated with several other comorbidities, including irritable bowel syndrome and systemic lupus erythematosus. […] Etiology, pathophysiology and biomarkers of interstitial cystitis/painful bladder syndrome.

• #56 Interstitial Cystitis (Painful Bladder Syndrome) | Enid Urology Associates

  https://www.enidurologyassociates.com/services-and-procedures/interstitial-cystitis

  Interstitial cystitis (IC) is a condition that results in recurring discomfort or pain in the bladder and the surrounding pelvic region. […] Because IC varies so much in symptoms and severity, most researchers believe it is not one, but several diseases. […] The term IC/PBS includes all cases of urinary pain that cant be attributed to other causes, such as infection or urinary stones. […] Many different problems can cause urgency, frequency, and bladder pain. Just a few of them are: infections, bowel disorders, endometriosis, bladder cancer. […] Sometimes the cause is hard to find. If all the test results are normal and all other diseases are ruled out, your doctor may find that you have IC/PBS. […] People with IC/PBS rarely have bladder pain all the time. […] Stress may bring on a flare-up of symptoms in someone who has IC/PBS. But stress does not cause a person to get IC/PBS.

• #57 Interstitial Cystitis – Harvard Health

  https://www.health.harvard.edu/a_to_z/interstitial-cystitis-a-to-z

  Interstitial cystitis is a puzzling bladder condition, in which the bladder wall becomes irritated or inflamed, causing pain and frequent or painful urination. […] The exact cause of interstitial cystitis remains a mystery, although researchers continue to investigate possible causes, such as unidentified bacteria, an allergic or immune system reaction, a toxic substance in the urine, or a neurological problem in the bladder wall. […] It is unknown why interstitial cystitis is more common in women. The disease is not known to be genetic (inherited) or caused by toxins in the environment. […] There is no one sign or test that can tell you immediately if you have interstitial cystitis. […] Since doctors do not know the cause of interstitial cystitis, there is no way to prevent it. […] No one therapy is so successful that it should always be tried first. […] There is no cure for interstitial cystitis and the prognosis is variable.

• #58

  https://link.springer.com/article/10.1007/s00404-017-4364-2

  Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic pain syndrome and a chronic inflammatory condition prevalent in women that leads to urgency, sleep disruption, nocturia and pain in the pelvic area, to the detriment of the sufferers quality of life. […] The etiology, exact diagnosis and epidemiology of IC/PBS are still not clearly understood. […] several etiological theories were investigated, such as permeability, glycosaminoglycans, mast cell, infection and neuroendocrine theory to find new diagnostic strategies and potential biomarkers. […] Due to the fact that this disease is of an intricate nature, and that many of its symptoms overlap with other concomitant diseases, it could be suggested to classify the patients with emphasis on the phenotype, as well as their symptom clusters, to tailor the diagnostic and management choices according to the observed biomarkers.

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