Materiały źródłowe

• #1 Cystitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482435/

  Cystitis refers to infection of the lower urinary tract, or more specifically, the urinary bladder. […] Acute cystitis is typically caused by a bacterial infection of the urinary bladder. […] Complicated cystitis is associated with risk factors that increase the likelihood and danger of the infection or the chances of failing antibiotic therapy. […] Cystitis usually develops due to the colonization of the periurethral mucosa by bacteria from the fecal or vaginal flora and the ascension of such pathogens to the urinary bladder. Uropathogens may have microbial virulence factors that allow them to escape host defenses and invade tissues in the urinary tract. […] The underlying host factors largely determine the pathogenesis of complicated UTIs. Impairment of the immune system and voiding dysfunction from autonomic neuropathy may predispose patients with diabetes to develop UTIs.

• #2 Pathology of Cystitis: Overview, Etiology, Gross Findings

  https://emedicine.medscape.com/article/2055346-overview

  Cystitis describes a broad range of diseases with diverse etiology and pathologic mechanisms but with similar clinical presentations. […] Bacterial cystitis is most commonly the result of an ascending infection through the urethra caused by the patients own enteric microbiota. […] The presence of anaerobic bacteria, such as Bacteroides fragilis, suggests communication between the intestinal and urinary tracts. […] The etiology of interstitial cystitis is not fully understood. […] Other etiologies have also been suggested, such as an unidentified infectious agent or a defective epithelial cell layer, with the latter allowing toxic substances to enter the bladder wall and trigger the symptoms. […] Furthermore, the role of mast cells and abnormalities in the central nervous system (CNS) has been proposed in the pathogenesis of interstitial cystitis as well.

• #3 Cystitis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Cystitis_pathophysiology

  Urine is normally sterile due to the low pH and unidirectional flow of urine that does not allow bacteria to grow and invade the urinary tract. Cystitis occurs when the normally sterile lower urinary tract (urethra and bladder) is either infected by bacteria or rarely a fungus, which leads to irritation and inflammation. […] The pathogenesis of complicated cystitis include obstruction and stasis of urine flow. Normal flow of urine washes away the pathogens and clears the tract. Obstruction leads to overdistension and bacterial growth is facilitated by the residual urine. Stasis of urine flow allows entry of pathogens into the urinary tract. […] Cystitis occurs when the normally sterile lower urinary tract (consisting of urethra and bladder) is infected by bacteria and becomes irritated and inflamed.

• #4 Cystitis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cystitis/symptoms-causes/syc-20371306

  Cystitis (sis-TIE-tis) is the medical term for inflammation of the bladder. Inflammation is when a part of your body is swollen and hot. It can also be painful. […] Most of the time, cystitis happens when there’s an infection caused by bacteria. This is called a urinary tract infection (UTI). […] Cystitis also may occur as a reaction to certain drugs or radiation therapy. […] Cystitis can also happen as a complication of another illness. […] UTIs typically occur when bacteria outside the body enter the urinary tract through the urethra and begin to multiply. Most cases of cystitis are caused by a type of Escherichia coli (E. coli) bacteria. But other types of bacteria can cause infections, too. […] Although bacterial infections are the most common cause of cystitis, a number of noninfectious factors also may cause the bladder to become inflamed.

• #5 Cystitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482435/

  Cystitis refers to infection of the lower urinary tract, or more specifically, the urinary bladder. […] Acute cystitis is typically caused by a bacterial infection of the urinary bladder. […] Complicated cystitis is associated with risk factors that increase the likelihood and danger of the infection or the chances of failing antibiotic therapy. […] Cystitis usually develops due to the colonization of the periurethral mucosa by bacteria from the fecal or vaginal flora and the ascension of such pathogens to the urinary bladder. Uropathogens may have microbial virulence factors that allow them to escape host defenses and invade tissues in the urinary tract. […] The underlying host factors largely determine the pathogenesis of complicated UTIs. Impairment of the immune system and voiding dysfunction from autonomic neuropathy may predispose patients with diabetes to develop UTIs.

• #6 Cystitis INFLAMMATION OF URINARY BLADDER | PPT

  https://www.slideshare.net/slideshow/cystitis-inflammation-of-urinary-bladder/39984445

  The bacteria that cause urinary tract infections typically enter the bladder via the urethra. However, infection may also occur via the blood or lymph. It is believed that the bacteria are usually transmitted to the urethra from the bowel, with females at greater risk due to their anatomy. After gaining entry to the bladder, E. Coli are able to attach to the bladder wall and form a biofilm that resists the body’s immune response. […] It is the most frequent bacterial infection in women. They occur most frequently between the ages of 16 and 35 years, with 10% of women getting an infection yearly and 60% having an infection at some point in their lives. Recurrences are common, with nearly half of people getting a second infection within a year. Urinary tract infections occur four times more frequently in females than males.

• #7 Cystitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482435/

  In renal insufficiency, accumulation of uremic toxins may reduce host defenses, and decreased renal blood flow may impair antimicrobial clearance. […] Kidney stones may cause an obstruction and provide a potential nidus of infection. […] In the setting of urinary catheterization, internal and external biofilms may form on the catheter, and pathogens may persist in retained pools of urine in the urinary bladder. […] The overwhelming identifiable bacteria causing most cases of cystitis is Escherichia coli (from 75% to 95% of cases). Other organisms causing cystitis include Klebsiella pneumoniae and Proteus mirabilis. […] Patients with recent hospitalizations or prior treatment for a UTI may present with Pseudomonas, enterococci, and staphylococci, such as S. saprophyticus.

• #8 Urinary tract infection – Wikipedia

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

  The bacteria that cause urinary tract infections typically enter the bladder via the urethra. However, infection may also occur via the blood or lymph. It is believed that the bacteria are usually transmitted to the urethra from the bowel, with females at greater risk due to their anatomy. After gaining entry to the bladder, E. Coli are able to attach to the bladder wall and form a biofilm that resists the body’s immune response. […] Escherichia coli is the single most common microorganism, followed by Klebsiella and Proteus spp., to cause urinary tract infection. Klebsiella and Proteus spp., are frequently associated with stone disease. The presence of Gram positive bacteria such as Enterococcus and Staphylococcus is increased. […] The increased resistance of urinary pathogens to quinolone antibiotics has been reported worldwide and might be the consequence of overuse and misuse of quinolones.

• #9 Pathology of Cystitis: Overview, Etiology, Gross Findings

  https://emedicine.medscape.com/article/2055346-overview

  Cystitis describes a broad range of diseases with diverse etiology and pathologic mechanisms but with similar clinical presentations. […] Bacterial cystitis is most commonly the result of an ascending infection through the urethra caused by the patients own enteric microbiota. […] The presence of anaerobic bacteria, such as Bacteroides fragilis, suggests communication between the intestinal and urinary tracts. […] The etiology of interstitial cystitis is not fully understood. […] Other etiologies have also been suggested, such as an unidentified infectious agent or a defective epithelial cell layer, with the latter allowing toxic substances to enter the bladder wall and trigger the symptoms. […] Furthermore, the role of mast cells and abnormalities in the central nervous system (CNS) has been proposed in the pathogenesis of interstitial cystitis as well.

• #10 Urinary tract infection – Wikipedia

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

  The bacteria that cause urinary tract infections typically enter the bladder via the urethra. However, infection may also occur via the blood or lymph. It is believed that the bacteria are usually transmitted to the urethra from the bowel, with females at greater risk due to their anatomy. After gaining entry to the bladder, E. Coli are able to attach to the bladder wall and form a biofilm that resists the body’s immune response. […] Escherichia coli is the single most common microorganism, followed by Klebsiella and Proteus spp., to cause urinary tract infection. Klebsiella and Proteus spp., are frequently associated with stone disease. The presence of Gram positive bacteria such as Enterococcus and Staphylococcus is increased. […] The increased resistance of urinary pathogens to quinolone antibiotics has been reported worldwide and might be the consequence of overuse and misuse of quinolones.

• #11 Cystitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482435/

  Cystitis refers to infection of the lower urinary tract, or more specifically, the urinary bladder. […] Acute cystitis is typically caused by a bacterial infection of the urinary bladder. […] Complicated cystitis is associated with risk factors that increase the likelihood and danger of the infection or the chances of failing antibiotic therapy. […] Cystitis usually develops due to the colonization of the periurethral mucosa by bacteria from the fecal or vaginal flora and the ascension of such pathogens to the urinary bladder. Uropathogens may have microbial virulence factors that allow them to escape host defenses and invade tissues in the urinary tract. […] The underlying host factors largely determine the pathogenesis of complicated UTIs. Impairment of the immune system and voiding dysfunction from autonomic neuropathy may predispose patients with diabetes to develop UTIs.

• #12 Cystitis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Cystitis_pathophysiology

  Urine is normally sterile due to the low pH and unidirectional flow of urine that does not allow bacteria to grow and invade the urinary tract. Cystitis occurs when the normally sterile lower urinary tract (urethra and bladder) is either infected by bacteria or rarely a fungus, which leads to irritation and inflammation. […] The pathogenesis of complicated cystitis include obstruction and stasis of urine flow. Normal flow of urine washes away the pathogens and clears the tract. Obstruction leads to overdistension and bacterial growth is facilitated by the residual urine. Stasis of urine flow allows entry of pathogens into the urinary tract. […] Cystitis occurs when the normally sterile lower urinary tract (consisting of urethra and bladder) is infected by bacteria and becomes irritated and inflamed.

• #13 Cystitis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Cystitis_pathophysiology

  The pathogenesis of complicated cystitis include obstruction and stasis of urine flow. […] Any process leading to the obstruction leads to over distension and so bacterial growth is facilitated by the residual urine. […] Stasis of urine flow allows entry of pathogens into the urinary tract and also hinders the natural preventive mechanism by which urine flushes away the pathogens and prevents colonisation in the urinary tract. […] The pathogenesis of Interstitial cystitis also known as bladder pain syndrome, includes: Epithelial dysfunction, Mast cell activation, Bladder sensory nerve up-regulation, Organ cross talk. […] Damage to the urothelium results in the production of cytokines which activate mast cells in the interstitium. […] The pathogenesis of cystitis cystica follows a positive feedback mechanism where with each infection there is a greater chance of subsequent changes in the bladder mucosa.

• #14 Cystitis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Cystitis_pathophysiology

  The pathogenesis of complicated cystitis include obstruction and stasis of urine flow. […] Any process leading to the obstruction leads to over distension and so bacterial growth is facilitated by the residual urine. […] Stasis of urine flow allows entry of pathogens into the urinary tract and also hinders the natural preventive mechanism by which urine flushes away the pathogens and prevents colonisation in the urinary tract. […] The pathogenesis of Interstitial cystitis also known as bladder pain syndrome, includes: Epithelial dysfunction, Mast cell activation, Bladder sensory nerve up-regulation, Organ cross talk. […] Damage to the urothelium results in the production of cytokines which activate mast cells in the interstitium. […] The pathogenesis of cystitis cystica follows a positive feedback mechanism where with each infection there is a greater chance of subsequent changes in the bladder mucosa.

• #15 Cystitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482435/

  Cystitis refers to infection of the lower urinary tract, or more specifically, the urinary bladder. […] Acute cystitis is typically caused by a bacterial infection of the urinary bladder. […] Complicated cystitis is associated with risk factors that increase the likelihood and danger of the infection or the chances of failing antibiotic therapy. […] Cystitis usually develops due to the colonization of the periurethral mucosa by bacteria from the fecal or vaginal flora and the ascension of such pathogens to the urinary bladder. Uropathogens may have microbial virulence factors that allow them to escape host defenses and invade tissues in the urinary tract. […] The underlying host factors largely determine the pathogenesis of complicated UTIs. Impairment of the immune system and voiding dysfunction from autonomic neuropathy may predispose patients with diabetes to develop UTIs.

• #16 Cystitis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Cystitis_pathophysiology

  Though the pathogenesis is not exactly understood, high tissue glucose content in a patient with diabetes mellitus and fermentation of glucose in urine are considered to be important mechanisms that facilitate invasion of gas forming bacteria. […] The following are some significant aspects in the pathogenesis of cystitis glandularis: This abnormal disorder of proliferation involves glandular metaplasia of transitional cells in the bladder epithelium. […] The pathogenesis of ketamine cystitis includes urothelial dysfunction by the following mechanisms: Inflammation mediated by mast cells, Increased expression of M3, Increased expression of B3-AR, Decreased expression of ZO-1 and E-cadherin in bladder mucosa, Increased TUNNEL expression and high Tryptase activity in the mucosa, Increased cell apoptosis in the urothelium.

• #17 Cystitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482435/

  In renal insufficiency, accumulation of uremic toxins may reduce host defenses, and decreased renal blood flow may impair antimicrobial clearance. […] Kidney stones may cause an obstruction and provide a potential nidus of infection. […] In the setting of urinary catheterization, internal and external biofilms may form on the catheter, and pathogens may persist in retained pools of urine in the urinary bladder. […] The overwhelming identifiable bacteria causing most cases of cystitis is Escherichia coli (from 75% to 95% of cases). Other organisms causing cystitis include Klebsiella pneumoniae and Proteus mirabilis. […] Patients with recent hospitalizations or prior treatment for a UTI may present with Pseudomonas, enterococci, and staphylococci, such as S. saprophyticus.

• #18 Cystitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482435/

  In renal insufficiency, accumulation of uremic toxins may reduce host defenses, and decreased renal blood flow may impair antimicrobial clearance. […] Kidney stones may cause an obstruction and provide a potential nidus of infection. […] In the setting of urinary catheterization, internal and external biofilms may form on the catheter, and pathogens may persist in retained pools of urine in the urinary bladder. […] The overwhelming identifiable bacteria causing most cases of cystitis is Escherichia coli (from 75% to 95% of cases). Other organisms causing cystitis include Klebsiella pneumoniae and Proteus mirabilis. […] Patients with recent hospitalizations or prior treatment for a UTI may present with Pseudomonas, enterococci, and staphylococci, such as S. saprophyticus.

• #19 Cystitis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cystitis/symptoms-causes/syc-20371306

  Some medicines, such as certain drugs used to treat cancer (chemotherapy), can cause inflammation of the bladder as the broken-down components of the drugs exit the body. […] Radiation treatment of the pelvic area can cause inflammatory changes in bladder tissue. […] Long-term use of a catheter can make bacterial infections and tissue damage more likely. […] Some people may be extra sensitive to chemicals found in certain products. […] Cystitis may sometimes occur as a complication of other conditions, such as diabetes, kidney stones, an enlarged prostate or spinal cord injury.

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

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

  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. […] Changes in this surface can cause permeability alterations that allow potassium ions to traverse the urothelium, depolarize sensory and motor nerves, and activate mast cells. This permeability dysfunction is manifested by increased urea absorption and positive potassium sensitivity tests in IC patients. […] 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. […] Substance P, a tachykinin released by activated C-fiber afferents, is involved in nociception in the central and peripheral nervous systems and also functions as an inflammatory mediator. Substance P release results in an inflammatory cascade with mast cell activation and up-regulation of adjacent nerves (sensory, autonomic, motor).

• #21 Mechanisms of oxidative stress in interstitial cystitis/bladder pain syndrome | Nature Reviews Urology

  https://www.nature.com/articles/s41585-023-00850-y

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder and/or pelvic pain, increased urinary urgency and frequency and nocturia. […] The pathophysiology of IC/BPS is poorly understood, and theories include chronic inflammation, autoimmune dysregulation, bacterial cystitis, urothelial dysfunction, deficiency of the glycosaminoglycan (GAG) barrier and urine cytotoxicity. […] Oxidative stress is implicated in the pathogenesis of IC/BPS as reactive oxygen species impair bladder function via their involvement in multiple molecular mechanisms. […] Kinase signalling pathways, nociceptive receptors, mast-cell activation, urothelial dysregulation and circadian rhythm disturbance have all been linked to reactive oxygen species and IC/BPS. […] However, further research is necessary to fully uncover the role of oxidative stress in the pathways driving IC/BPS pathogenesis. […] As IC/BPS might be multifactorial, future research should target different implicated pathways simultaneously and study the role of reactive oxygen species as a root cause in IC/BPS.

• #22 Pathomechanism of Interstitial Cystitis/Bladder Pain Syndrome and Mapping the Heterogeneity of Disease

  https://www.einj.org/journal/view.php?doi=10.5213/inj.1632712.356

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. […] It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. […] Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. […] The pathophysiology of IC/BPS might involve chronic inflammation, increased apoptosis, urothelial dysfunction, and CNS sensitization. […] Bladder urothelium denudation and thinning, aberrant synthesis of proteoglycans, cell adhesive proteins and tight junction proteins, and bacterial defence molecules were found in the IC/BPS bladders.

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

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

  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. […] Changes in this surface can cause permeability alterations that allow potassium ions to traverse the urothelium, depolarize sensory and motor nerves, and activate mast cells. This permeability dysfunction is manifested by increased urea absorption and positive potassium sensitivity tests in IC patients. […] 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. […] Substance P, a tachykinin released by activated C-fiber afferents, is involved in nociception in the central and peripheral nervous systems and also functions as an inflammatory mediator. Substance P release results in an inflammatory cascade with mast cell activation and up-regulation of adjacent nerves (sensory, autonomic, motor).

• #24 Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/10/10/2380

  The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is multifactorial. Identifying the clinical characteristics and cystoscopic findings of bladder-centered IC/BPS facilitates optimal treatment strategies targeting the diseased urinary bladder. […] The known pathological findings from the bladders of IC/BPS patients included urothelial denudation, chronic inflammation, and sensory afferent activation. […] The prominent pathological findings of IC/BPS bladders include chronic inflammation and urothelial denudation. Inflammation is higher in bladders with Hunner’s lesions (HIC) compared with inflammation in non-Hunner’s IC (NHIC). […] Increased microvascular endothelial cell apoptosis in IC bladders causes glomerulations, and impaired urothelial homeostasis is associated with chronic bladder inflammation.

• #25 Interstitial Cystitis: Urgency and Frequency Syndrome | AAFP

  https://www.aafp.org/pubs/afp/issues/2001/1001/p1199.html

  Interstitial cystitis is a chronic, severely debilitating disease of the urinary bladder. […] While the exact cause of interstitial cystitis is not known, it is probably related to many factors, including autoimmune, allergic and infectious etiologies. […] According to one widely held theory, the symptoms of interstitial cystitis originate from a defect in the glycosaminoglycan component of the mucin layer that covers and protects the bladder urothelium. […] A deficiency of this layer is thought to cause interstitial cystitis. […] Irritating substances in the urine may leak through the urothelium, causing inflammation, tissue irritation and injury, mast cell degranulation and sensory nerve depolarization, which result in the urinary urgency, frequency and pain of interstitial cystitis.

• #26 Interstitial cystitis – Wikipedia

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

  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. […] Evidence from clinical and laboratory studies confirms that mast cells play a central role in IC/BPS possibly due to their ability to release histamine and cause pain, swelling, scarring, and interfere with healing. […] Research has shown a proliferation of nerve fibers is present in the bladders of people with IC which is absent in the bladders of people who have not been diagnosed with IC. […] 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 bladdera breakdown of the bladder lining (also known as the adherence theory).

• #27 Pathomechanism of Interstitial Cystitis/Bladder Pain Syndrome and Mapping the Heterogeneity of Disease

  https://www.einj.org/journal/view.php?doi=10.5213/inj.1632712.356

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. […] It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. […] Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. […] The pathophysiology of IC/BPS might involve chronic inflammation, increased apoptosis, urothelial dysfunction, and CNS sensitization. […] Bladder urothelium denudation and thinning, aberrant synthesis of proteoglycans, cell adhesive proteins and tight junction proteins, and bacterial defence molecules were found in the IC/BPS bladders.

• #28 :: International Neurourology Journal

  https://www.einj.org/m/journal/view.php?number=621

  Increased apoptosis cells and decreased proliferative cells were noted in IC bladder urothelium compared with the control group. […] Increased levels of the apoptotic signaling molecules, including Bax, cleaved caspase-3, and Bad were elevated in the IC/BPS bladder tissues. […] Urothelial barrier dysfunction may lead to abnormal urinary solutes migration, such as potassium, which depolarizes muscle and nerves, and then causes tissue injury and bladder pain. […] The pathophysiology of IC/BPS urothelium involves an aberrant differentiation program that results in altered synthesis of proteoglycans, tight junction proteins, cell adhesive proteins, and bacterial defense molecules such as GP51. […] Bladder urothelium denudation and thinning, aberrant synthesis of proteoglycans, cell adhesive proteins and tight junction proteins, and bacterial defence molecules were found in the IC/BPS bladders.

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

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

  Mast cells contain vasoactive and inflammatory mediators, (eg, histamine, leukotrienes, prostaglandins, and tryptases), and they play a central role in the pathogenesis of neuroinflammatory conditions, including IC. […] 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. […] 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. Changes in urothelial permeability, sensory nerve stimulation, and mast cell activation are interrelated with multiple positive and negative feedback loops occurring simultaneously. […] The multifactorial etiology of IC and its complex, interrelated pathogenesis involving the bladder urothelium, sensory nerves, and mast cells are being increasingly defined.

• #30 Interstitial Cystitis: Urgency and Frequency Syndrome | AAFP

  https://www.aafp.org/pubs/afp/issues/2001/1001/p1199.html

  Another working theory of interstitial cystitis etiology includes mast cell abnormalities. […] Increased numbers of submucosal mast cells are found in these patients. […] Antigenic exposure of mast cells causes the release of pharmacologically active mediators (e.g., histamine, prostaglandins, leukotrienes and tryptases) that have a significant effect on smooth muscle, vascular epithelium and inflammation.

• #31

  https://discovery.ucl.ac.uk/id/eprint/10121271/

  Aberrant urothelial HLA-DR expression was found in all but one of the IC cases in which the urothelium was not denuded. […] Furthermore, the urothelium and submucosa in IC was infiltrated by CD4+, CD8+ and T cells, plasma cells, mast cells and macrophages. […] The precise aetiology of IC remains obscure although this study has revealed a genetic predisposition to the development of IC and has demonstrated immunological autoreactive mechanisms in the pathogenesis of this condition.

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

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

  Chronic inflammation of the bladder wall is the fundamental pathophysiology of IC/BPS. […] Increased expression of the inflammatory marker tryptase in the suburothelium has been associated with the increased expression of the apoptotic marker terminal deoxynucleotidyl transferase, decreased expression of the proliferation marker Ki-67, and decreased expression of the adhesive proteins E-cadherin and zonula occludens-1. […] The medical treatments used to treat chronic inflammation in patients with IC/BPS frequently include non-steroidal anti-inflammatory drugs (NSAIDs), pain killers, COX-2 inhibitors, and β-3 adrenoceptor agonists. […] Intravesical BoNT-A injection was first used in the treatment of neurogenic and idiopathic overactive bladders. […] The therapeutic effects of BoNT-A injections for IC/BPS were found to be superior to those of a placebo with some durability.

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

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

  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. […] Changes in this surface can cause permeability alterations that allow potassium ions to traverse the urothelium, depolarize sensory and motor nerves, and activate mast cells. This permeability dysfunction is manifested by increased urea absorption and positive potassium sensitivity tests in IC patients. […] 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. […] Substance P, a tachykinin released by activated C-fiber afferents, is involved in nociception in the central and peripheral nervous systems and also functions as an inflammatory mediator. Substance P release results in an inflammatory cascade with mast cell activation and up-regulation of adjacent nerves (sensory, autonomic, motor).

• #34 Internet Scientific Publications

  https://ispub.com/IJU/7/1/3195

  Certain inflammatory mediators, such as substance P and bradykinin also function as nociceptive neurotransmitters. […] Increased numbers of mast cells have been demonstrated within the detrusor layer of the bladder in IC patients. […] Many of the clinical features of IC suggest that autoimmunity may play a role in the chronic inflammatory component of the disease. […] The development of new and more effective treatments modalities for IC has been severely hampered by the lack of experimental models. […] The use of in vitro models examine various elements of the disease has been quite useful, although they do have some inherent limitations. […] Techniques of re-creating disease conditions are becoming more and more realistic however, and with each new study, our etiological picture becomes more clear.

• #35 Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/10/10/2380

  Chronic pain in patients with IC/BPS is likely caused by central nervous system (CNS) sensitization and activation of sensory afferent nerves. […] Bladder dysfunction might originate from chronic inflammation, causing urothelial defects and more tissue reactions, subsequently leading to inflammation of the CNS. […] The fundamental pathophysiology of IC/BPS includes chronic bladder inflammation, increased urothelial cell apoptosis, decreased urothelial proliferation and differentiation, and defects in the urothelial barrier.

• #36 Interstitial cystitis – Wikipedia

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

  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. […] Evidence from clinical and laboratory studies confirms that mast cells play a central role in IC/BPS possibly due to their ability to release histamine and cause pain, swelling, scarring, and interfere with healing. […] Research has shown a proliferation of nerve fibers is present in the bladders of people with IC which is absent in the bladders of people who have not been diagnosed with IC. […] 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 bladdera breakdown of the bladder lining (also known as the adherence theory).

• #37 Pathomechanism of Interstitial Cystitis/Bladder Pain Syndrome and Mapping the Heterogeneity of Disease

  https://www.einj.org/journal/view.php?doi=10.5213/inj.1632712.356

  The apoptosis in IC/BPS bladders might be due to upregulation of inflammatory signals. […] Urothelial barrier dysfunction may lead to abnormal urinary solutes migration, such as potassium, which depolarizes muscle and nerves, and then causes tissue injury and bladder pain. […] Increased levels of urothelial cell apoptosis and decreased proliferation have been noted, suggesting an altered homeostasis in IC/BPS urothelium. […] The involvement of IC/BPS in systemic functional somatic syndrome and other pelvic organ diseases might also subdivide subtypes of IC/BPS. […] Increased sensory afferent activity including pain associated C-fibers in chronic IC will further cause bladder pain with a full bladder, especially in ulcer type IC/BPS. […] It has been suggested that immunological reaction occurs in IC/BPS bladders.

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

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

  Mast cells contain vasoactive and inflammatory mediators, (eg, histamine, leukotrienes, prostaglandins, and tryptases), and they play a central role in the pathogenesis of neuroinflammatory conditions, including IC. […] 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. […] 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. Changes in urothelial permeability, sensory nerve stimulation, and mast cell activation are interrelated with multiple positive and negative feedback loops occurring simultaneously. […] The multifactorial etiology of IC and its complex, interrelated pathogenesis involving the bladder urothelium, sensory nerves, and mast cells are being increasingly defined.

• #39 Pathology of Cystitis: Overview, Etiology, Gross Findings

  https://emedicine.medscape.com/article/2055346-overview

  Gene expression profiles from bladder biopsies in patients with ulcerative interstitial cystitis have shown a similar expression pattern to those of patients with immune system, lymphatic, and autoimmune diseases. The majority of the upregulated genes were expressed in the leukocytes, suggesting that leukocyte invasion of the bladder wall is important in the pathomechanism of ulcerative interstitial cystitis. […] Heterozygous polymorphisms in the drug-metabolizing enzyme alleles ALDH3A1*2 and ALDH1A1*2, members of the aldehyde dehydrogenase gene family, have been linked to an increased risk of developing hemorrhagic cystitis and liver toxicity in patients treated with high doses of combination chemotherapy, including cyclophosphamide, thiotepa, and carboplatin.

• #40

  https://discovery.ucl.ac.uk/id/eprint/10121271/

  The role of the immune system in the pathogenesis of interstitial cystitis. […] Interstitial cystitis (IC) is a chronic debilitating condition predominantly affecting middle-aged females which presents with suprapubic pain and urinary frequency. […] Chronic inflammatory cell infiltrate within bladder biopsies suggests an immunological aetiopathogenesis for IC but this has not previously been investigated in great detail. […] The presence of chronic inflammation without evidence of an infective agent, the high incidence in middle-aged females and association with conditions such as Hashimoto’s thyroiditis are features shared by IC and autoimmune diseases. […] In autoimmune diseases target cell destruction is initiated by abnormal surface expression of class II (HLA-DR) molecules with antigen which activates CD4+ T cells which in turn starts the cascade of immune autoreactivity, ultimately leading to destruction of target cells.

• #41

  https://discovery.ucl.ac.uk/id/eprint/10121271/

  Aberrant urothelial HLA-DR expression was found in all but one of the IC cases in which the urothelium was not denuded. […] Furthermore, the urothelium and submucosa in IC was infiltrated by CD4+, CD8+ and T cells, plasma cells, mast cells and macrophages. […] The precise aetiology of IC remains obscure although this study has revealed a genetic predisposition to the development of IC and has demonstrated immunological autoreactive mechanisms in the pathogenesis of this condition.

• #42 Internet Scientific Publications

  https://ispub.com/IJU/7/1/3195

  One of the leading theories of pathogenesis is that the urine of IC patients is itself carrying a toxic substance accounting for the disorder. […] Other studies have shown the presence of antiproliferative factor (APF), in the urine of IC patients that inhibits the proliferation of normal human bladder epithelial cells in vitro. […] The theory that IC urine contains toxic factors is also supported by the fact that bladder tissues treated with urine from IC patients showed increased expression of a stress protein (heat shock protein, 72 kDa HSP). […] A defect in this protective layer could permit pathogens leak into the subepithelial space and the muscularis, possibly injuring muscle and/or initiating sensory stimulation causing symptoms of IC. […] It has been proposed that IC may develop as a consequence of urothelial injury that persists after infectious agents are no longer present.

• #43 Dysregulation of bladder corticotropin-releasing hormone receptor in the pathogenesis of human interstitial cystitis/bladder pain syndrome | Scientific Reports

  https://www.nature.com/articles/s41598-019-55584-y

  Stress is associated with exacerbated symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). […] To investigate the mechanism of stress implicated on IC/BPS, we investigated expression of stress-response receptor corticotropin-releasing hormone receptor (CRHR) in bladder from IC/BPS patients. […] Our results indicate dysregulation of bladder CRHR1 and CRHR2 in patients with IC/BPS, and suggest CRH signaling may be associated with IC/BPS symptoms. […] Recent studies revealed urothelial function abnormality in the pathogenesis of IC/BPS involving several possible mechanisms. […] The expression of CRHR2 was also significantly correlated with clinical symptoms in IC/BPS patients. […] Our findings suggest the CRH pathway may be involved in the mechanism of neurogenic inflammation in IC/BPS bladder.

• #44 Dysregulation of bladder corticotropin-releasing hormone receptor in the pathogenesis of human interstitial cystitis/bladder pain syndrome | Scientific Reports

  https://www.nature.com/articles/s41598-019-55584-y

  Our current study not only showed upregulation of CRHR1 in IC/BPS bladder, but also revealed the expression of CRHR1 was located in the activated mast cells. […] The changes in CRHR1 and CRHR2 seem to be more predominant in HIC bladder. […] Thus it is likely that changes in CRHR expression in the bladder might play an important role in human IC/BPS, especially in patients with HIC. […] The altered receptor expression suggests that CRH-related peptides within the bladder mucosa may play a role in IC/BPS pathophysiology.

• #45 Mechanisms of oxidative stress in interstitial cystitis/bladder pain syndrome | Nature Reviews Urology

  https://www.nature.com/articles/s41585-023-00850-y

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder and/or pelvic pain, increased urinary urgency and frequency and nocturia. […] The pathophysiology of IC/BPS is poorly understood, and theories include chronic inflammation, autoimmune dysregulation, bacterial cystitis, urothelial dysfunction, deficiency of the glycosaminoglycan (GAG) barrier and urine cytotoxicity. […] Oxidative stress is implicated in the pathogenesis of IC/BPS as reactive oxygen species impair bladder function via their involvement in multiple molecular mechanisms. […] Kinase signalling pathways, nociceptive receptors, mast-cell activation, urothelial dysregulation and circadian rhythm disturbance have all been linked to reactive oxygen species and IC/BPS. […] However, further research is necessary to fully uncover the role of oxidative stress in the pathways driving IC/BPS pathogenesis. […] As IC/BPS might be multifactorial, future research should target different implicated pathways simultaneously and study the role of reactive oxygen species as a root cause in IC/BPS.

• #46

  https://link.springer.com/article/10.1007/s11884-023-00713-7

  The pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) is still unclear. […] However, viral infection in the bladder might be a pathogenic factor for IC/BPS. […] The presence of urinary virus in the patients with IC/BPS suggested that viral infection might be a pathogenic factor in patients with IC/BPS. Molecular evidence from IC/BPS bladder tissue also showed that viral infection may involve the pathogenesis of IC/BPS. […] Further studies are needed to clarify the mechanism.

• #47 Chemical hemorrhagic cystitis: Diagnostic and therapeutic pitfalls (Review)

  https://www.spandidos-publications.com/10.3892/etm.2021.10056

  Chemical cystitis (CC) is an inflammation of the bladder caused by various chemical agents ingested intentionally or accidentally. […] CC is caused by different chemical agents ingested orally, intravenously, through instillation therapy, or topical contiguity. […] CC is attributed to chemotherapeutic or immunologic drug administration such as cyclophosphamide, medication administered for different pathologies, or the use of certain anesthetic drugs in a recreational manner, such as ketamine. […] CC is noninfectious cystitis, and it is caused by chemical irritation of the bladder mucosa. […] CC tends to be more aggressive than infectious cystitis, with more severe irritative lower urinary tract symptoms (LUTS), hematuria, and bladder pain. […] Cyclophosphamide is an oxazophosphorine compound, and its urinary tract toxicity is proven to be dose-related.

• #48 Hemorrhagic Cystitis: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/2056130-overview

  Hemorrhagic cystitis results from damage to the bladder’s transitional epithelium and blood vessels by toxins, viruses, radiation, drugs (in particular, chemotherapeutic drugs), bacterial infections, or other disease processes. Histologically, the bladder wall demonstrates nonspecific findings of intense inflammatory infiltrates, chronic inflammation, and fibrosis. […] Cyclophosphamide is the most common cause of hemorrhagic cystitis in the oncologic population. The urotoxicity observed with cyclophosphamide is due to its liver metabolite acrolein, which is excreted in the urine. Although the entire urothelium is at risk of urotoxicity, the bladder, which serves as a reservoir, is most frequently affected, because the contact time between acrolein and the urothelium is greatest at this site.

• #49 Chemical hemorrhagic cystitis: Diagnostic and therapeutic pitfalls (Review)

  https://www.spandidos-publications.com/10.3892/etm.2021.10056

  Both cyclophosphamide and iphosphamide express a corrosive liver product called acrolein, which is filtered by the kidneys and consequently accumulates in the bladder. […] Acrolein induces a reaction with pyroptotic effects in the urothelium resulting in ulceration and exposure of the muscularis mucosa and the blood vessels. […] The intravesical instillation with bacillus Calmette-Guerin (BCG) is the most effective prophylactic immunotherapy for intermediate or high-risk non-muscle-invasive bladder cancer. […] It is considered that a breach in the glycosaminoglycans GAG layer, which covers the urothelium in the bladder, is the first step of the CC physiopathologic mechanism. […] Ketamine-induced CC generates more severe LUTS and smaller bladder capacity, conditions that are even more severe than bladder pain syndrome or interstitial cystitis.

• #50 Pathology of Cystitis: Overview, Etiology, Gross Findings

  https://emedicine.medscape.com/article/2055346-overview

  Gene expression profiles from bladder biopsies in patients with ulcerative interstitial cystitis have shown a similar expression pattern to those of patients with immune system, lymphatic, and autoimmune diseases. The majority of the upregulated genes were expressed in the leukocytes, suggesting that leukocyte invasion of the bladder wall is important in the pathomechanism of ulcerative interstitial cystitis. […] Heterozygous polymorphisms in the drug-metabolizing enzyme alleles ALDH3A1*2 and ALDH1A1*2, members of the aldehyde dehydrogenase gene family, have been linked to an increased risk of developing hemorrhagic cystitis and liver toxicity in patients treated with high doses of combination chemotherapy, including cyclophosphamide, thiotepa, and carboplatin.

• #51 Hemorrhagic Cystitis: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/2056130-overview

  Radiation-induced hemorrhagic cystitis is most common in patients receiving pelvic irradiation. Hematuria may develop acutely during radiation treatment or months to years later. The symptoms of radiation cystitis are caused by a microscopic progressive obliterative endarteritis that leads to mucosal ischemia. The ischemic bladder mucosa then ulcerates and bleeding ensues. Neovascular ingrowth to the damaged area, as shown in the images below, then occurs, causing the characteristic vascular blush on cystoscopic evaluation. The new vessels are more fragile and may leak (petechiae) with bladder distention, minor trauma, infection, or any mucosal irritation. […] Hemorrhagic cystitis has both infectious and noninfectious causes. Although the noninfectious causes of hemorrhagic cystitis vary, this condition most commonly develops as a complication of pelvic radiation or from toxicity related to the use of certain chemotherapeutic drugs (eg, cyclophosphamide, ifosfamide). Less commonly, exposure to certain industrial chemicals, such as aniline or toluidine derivatives, causes hemorrhagic cystitis. […] Mucosal ischemia secondary to radiation injury results from endarteritis inducing hypoxic surface damage, ulceration, and bleeding. The incidence in the pediatric population is less than that in adults. Slightly less than 50% of these patients develop diffuse hematuria.

• #52 Hemorrhagic Cystitis: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/2056130-overview

  Radiation-induced hemorrhagic cystitis is most common in patients receiving pelvic irradiation. Hematuria may develop acutely during radiation treatment or months to years later. The symptoms of radiation cystitis are caused by a microscopic progressive obliterative endarteritis that leads to mucosal ischemia. The ischemic bladder mucosa then ulcerates and bleeding ensues. Neovascular ingrowth to the damaged area, as shown in the images below, then occurs, causing the characteristic vascular blush on cystoscopic evaluation. The new vessels are more fragile and may leak (petechiae) with bladder distention, minor trauma, infection, or any mucosal irritation. […] Hemorrhagic cystitis has both infectious and noninfectious causes. Although the noninfectious causes of hemorrhagic cystitis vary, this condition most commonly develops as a complication of pelvic radiation or from toxicity related to the use of certain chemotherapeutic drugs (eg, cyclophosphamide, ifosfamide). Less commonly, exposure to certain industrial chemicals, such as aniline or toluidine derivatives, causes hemorrhagic cystitis. […] Mucosal ischemia secondary to radiation injury results from endarteritis inducing hypoxic surface damage, ulceration, and bleeding. The incidence in the pediatric population is less than that in adults. Slightly less than 50% of these patients develop diffuse hematuria.

• #53 Chemical hemorrhagic cystitis: Diagnostic and therapeutic pitfalls (Review)

  https://www.spandidos-publications.com/10.3892/etm.2021.10056

  Both cyclophosphamide and iphosphamide express a corrosive liver product called acrolein, which is filtered by the kidneys and consequently accumulates in the bladder. […] Acrolein induces a reaction with pyroptotic effects in the urothelium resulting in ulceration and exposure of the muscularis mucosa and the blood vessels. […] The intravesical instillation with bacillus Calmette-Guerin (BCG) is the most effective prophylactic immunotherapy for intermediate or high-risk non-muscle-invasive bladder cancer. […] It is considered that a breach in the glycosaminoglycans GAG layer, which covers the urothelium in the bladder, is the first step of the CC physiopathologic mechanism. […] Ketamine-induced CC generates more severe LUTS and smaller bladder capacity, conditions that are even more severe than bladder pain syndrome or interstitial cystitis.

• #54 Drug-Related Cystitis: An Overview | IntechOpen

  https://www.intechopen.com/chapters/86970

  Cystitis is an inflammatory condition of the urinary bladder with infectious or noninfectious aetiologies. […] Drug-related cystitis is a type of urotoxicity of drugs, which is a commonly underreported condition leading to impaired quality of patients life, discontinuation of medication and non-compliance. […] Drug-related cystitis can occur in several forms ranging from mild urinary symptoms to gross haematuria, which can be challenging for physicians to treat. […] There is currently no standard to diagnose drug-related cystitis, in which its diagnosis usually relies on cystoscopy and clinical presentation along with the exclusion of other aetiologies such as infection, radiation-induced cystitis and metastasis. […] The pathogenesis of ketamine-induced cystitis is complicated and involves various mechanisms underlying the urothelial disruption, apoptosis, inflammation and fibrosis in the lamina propria; however, the precise mechanism remains largely unknown.

• #55 Drug-Related Cystitis: An Overview | IntechOpen

  https://www.intechopen.com/chapters/86970

  The direct toxic effects of ketamine and norketamine on urothelium have been suggested to contribute to bladder damage. […] The aetiology is unclear; however, it can result from the direct toxic effect of tiaprofenic acid on the urothelium and a delayed hypersensitive immune response accompanied by the late onset of the symptoms. […] Cystitis induced by BCG has been shown to occur as a result of chemical or bacterial aetiology. […] Cystitis is considered to be unusual for being a side effect of drugs, except with some chemotherapeutics. […] Therefore, drug-related cystitis is likely to be a less recognised and underestimated condition that leads to impaired quality of patients life, discontinuation of medication and non-compliance.

• #56 Ketamine bladder | Radiology Case | Radiopaedia.org

  https://radiopaedia.org/cases/ketamine-bladder-1

  Cystoscopy typically reveals ulcerative cystitis; ureteral involvement presents as diffuse edema. […] Ketamine induced uropathy (KIU) is a dose-dependent condition associated with chronic ketamine abuse, primarily affecting young adults with storage low urinary tract symptoms. […] First-line management includes ketamine cessation. Medical therapy (anti-inflammatories, analgesics, anticholinergics) is effective in early, non-fibrotic stages. Refractory cases may require intravesical botulinum toxin-A injections, hydrodistension, or hyaluronic acid instillation. Surgical intervention is indicated for persistent symptoms with bladder fibrosis or upper tract involvement.

• #57

  https://journals.lww.com/co-infectiousdiseases/fulltext/2007/02000/interstitial_cystitis_pathogenesis_and_treatment.14.aspx

  Interstitial cystitis is manifested by sensory hypersensitivity. A small volume of urine will be associated with an exaggerated sensation of pain or pressure and urinary urgency. […] The pathogenesis of interstitial cystitis remains uncertain and the illness has significant diversity. Additional research is needed to establish subtypes that share common processes that can be targeted for treatment as a single effective therapy for the condition remains elusive.

• #58 Molecular Basis of Acute Cystitis Reveals Susceptibility Genes and Immunotherapeutic Targets | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005848

  Tissue damage is usually regarded as a necessary price to pay for successful elimination of pathogens by the innate immune defense. […] Here, we identify acute cystitis as an Interleukin-1 beta (IL-1)-driven, hyper-inflammatory condition of the infected urinary bladder and IL-1 receptor blockade as a novel therapeutic strategy. […] The most severe form of acute cystitis was detected in mice lacking the inflammasome constituents ASC or NLRP-3. […] IL-1 processing was hyperactive in these mice, due to a new, non-canonical mechanism involving the matrix metalloproteinase 7- (MMP-7). […] The resulting IL-1 hyper-activation loop included a large number of IL-1-dependent pro-inflammatory genes and the IL-1 receptor antagonist Anakinra inhibited their expression and rescued susceptible Asc-/- mice from bladder pathology.

• #59 Molecular Basis of Acute Cystitis Reveals Susceptibility Genes and Immunotherapeutic Targets | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005848

  Tissue damage is usually regarded as a necessary price to pay for successful elimination of pathogens by the innate immune defense. […] Here, we identify acute cystitis as an Interleukin-1 beta (IL-1)-driven, hyper-inflammatory condition of the infected urinary bladder and IL-1 receptor blockade as a novel therapeutic strategy. […] The most severe form of acute cystitis was detected in mice lacking the inflammasome constituents ASC or NLRP-3. […] IL-1 processing was hyperactive in these mice, due to a new, non-canonical mechanism involving the matrix metalloproteinase 7- (MMP-7). […] The resulting IL-1 hyper-activation loop included a large number of IL-1-dependent pro-inflammatory genes and the IL-1 receptor antagonist Anakinra inhibited their expression and rescued susceptible Asc-/- mice from bladder pathology.

• #60 Molecular Basis of Acute Cystitis Reveals Susceptibility Genes and Immunotherapeutic Targets | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005848

  Finally, elevated levels of IL-1 and MMP-7 were detected in patients with acute cystitis, suggesting a potential role as biomarkers and immunotherapeutic targets. […] This study examined how innate immune response genes influence the outcome of bladder infection and the pathogenesis of acute cystitis. […] We identify acute cystitis as an IL-1-driven, hyper-inflammatory disease, possibly related to other hyper-inflammatory disorders. […] Using IL-1 and MMP-7 as targets for immunotherapy, we succeeded in protecting susceptible Asc-/- mice against acute cystitis, confirming the potential of immunotherapy for this indication. […] Major, genotype-specific differences in bladder inflammation and pathology were detected after seven days. […] These studies identify genetic determinants of host susceptibility to acute cystitis.

• #61 Molecular Basis of Acute Cystitis Reveals Susceptibility Genes and Immunotherapeutic Targets | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005848

  The results identify IL-1 driven pro-inflammatory genes that are activated, exclusively in Asc-/- and Nlrp3-/- mice with severe bladder pathology. […] The results confirm the importance of IL-1 and MMP-7 for the pathogenesis of acute cystitis and identify these molecules as functional targets for immunomodulatory therapy. […] The results show that patients with acute cystitis have more elevated concentrations of IL-1 and MMP-7 in urine, than patients with ABU, identifying IL-1 and MMP-7 as potential biomarkers of acute cystitis.

• #62 Etiology, pathogenesis, diagnosis and treatment of encrusted cystitis and pyelitis: Review of the problem from a historical perspective

  https://www.scielo.org.mx/scielo.php?pid=S2007-40852024000100005&script=sci_arttext

  Etiology, pathogenesis, diagnosis and treatment of encrusted cystitis and pyelitis: Review of the problem from a historical perspective […] Encrusted cystitis and pyelitis share many similarities regarding etiology, pathogenesis, diagnosis and treatment. These processes usually occur on previously injured urological tissue with the participation of an infection by urease-producing bacteria. At present Corynebacterium urealyticum, a highly antibiotic-resistant bacteria, appears to be the pathogen most often involved in these processes. […] Encrusted cystitis is a chronic disease of the urinary bladder with inflammation and calcareous deposits encrusted in the mucosa, generally accompanied by alkaline urine, sometimes with a strong ammonia-like odor, leukocyturia and, occasionally, hematuria of varying intensity.

• #63 Etiology, pathogenesis, diagnosis and treatment of encrusted cystitis and pyelitis: Review of the problem from a historical perspective

  https://www.scielo.org.mx/scielo.php?pid=S2007-40852024000100005&script=sci_arttext

  Encrusted cystitis and encrusted pyelitis share very common aspects in terms of etiology, pathogenesis, diagnosis and treatment, differing only in the location of the lesions, although sometimes both processes may occur together. […] Both cystitis and pyelitis are associated with deposits of calcareous salts (triple phosphate), causing severe lesions that are difficult to repair. These deposits are caused by urease, an enzyme of microbial origin. By hydrolyzing urea into CO2 and ammonia (NH3), urease alkalinizes the urine by sequestering H+ ions, leading to the formation of ammonium (NH4+). […] The role of urease in the genesis of struvite stones has been clearly demonstrated in experimental models, even by intrarenal injection of this enzyme alone. […] The first paper in which a clear definition of encrusted cystitis is given, describing the signs and symptoms, cystoscopic findings, histopathology, pathogenesis, prognosis, diagnosis and treatment of this entity was published by Franoise in 1914.

• #64 Etiology, pathogenesis, diagnosis and treatment of encrusted cystitis and pyelitis: Review of the problem from a historical perspective

  https://www.scielo.org.mx/scielo.php?pid=S2007-40852024000100005&script=sci_arttext

  Etiology, pathogenesis, diagnosis and treatment of encrusted cystitis and pyelitis: Review of the problem from a historical perspective […] Encrusted cystitis and pyelitis share many similarities regarding etiology, pathogenesis, diagnosis and treatment. These processes usually occur on previously injured urological tissue with the participation of an infection by urease-producing bacteria. At present Corynebacterium urealyticum, a highly antibiotic-resistant bacteria, appears to be the pathogen most often involved in these processes. […] Encrusted cystitis is a chronic disease of the urinary bladder with inflammation and calcareous deposits encrusted in the mucosa, generally accompanied by alkaline urine, sometimes with a strong ammonia-like odor, leukocyturia and, occasionally, hematuria of varying intensity.

• #65 Etiology, pathogenesis, diagnosis and treatment of encrusted cystitis and pyelitis: Review of the problem from a historical perspective

  https://www.scielo.org.mx/scielo.php?pid=S2007-40852024000100005&script=sci_arttext

  Encrusted cystitis and encrusted pyelitis share very common aspects in terms of etiology, pathogenesis, diagnosis and treatment, differing only in the location of the lesions, although sometimes both processes may occur together. […] Both cystitis and pyelitis are associated with deposits of calcareous salts (triple phosphate), causing severe lesions that are difficult to repair. These deposits are caused by urease, an enzyme of microbial origin. By hydrolyzing urea into CO2 and ammonia (NH3), urease alkalinizes the urine by sequestering H+ ions, leading to the formation of ammonium (NH4+). […] The role of urease in the genesis of struvite stones has been clearly demonstrated in experimental models, even by intrarenal injection of this enzyme alone. […] The first paper in which a clear definition of encrusted cystitis is given, describing the signs and symptoms, cystoscopic findings, histopathology, pathogenesis, prognosis, diagnosis and treatment of this entity was published by Franoise in 1914.

• #66 Pathology of Cystitis: Overview, Etiology, Gross Findings

  https://emedicine.medscape.com/article/2055346-overview

  Cystitis describes a broad range of diseases with diverse etiology and pathologic mechanisms but with similar clinical presentations. […] Bacterial cystitis is most commonly the result of an ascending infection through the urethra caused by the patients own enteric microbiota. […] The presence of anaerobic bacteria, such as Bacteroides fragilis, suggests communication between the intestinal and urinary tracts. […] The etiology of interstitial cystitis is not fully understood. […] Other etiologies have also been suggested, such as an unidentified infectious agent or a defective epithelial cell layer, with the latter allowing toxic substances to enter the bladder wall and trigger the symptoms. […] Furthermore, the role of mast cells and abnormalities in the central nervous system (CNS) has been proposed in the pathogenesis of interstitial cystitis as well.

• #67 Cystitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482435/

  Cystitis refers to infection of the lower urinary tract, or more specifically, the urinary bladder. […] Acute cystitis is typically caused by a bacterial infection of the urinary bladder. […] Complicated cystitis is associated with risk factors that increase the likelihood and danger of the infection or the chances of failing antibiotic therapy. […] Cystitis usually develops due to the colonization of the periurethral mucosa by bacteria from the fecal or vaginal flora and the ascension of such pathogens to the urinary bladder. Uropathogens may have microbial virulence factors that allow them to escape host defenses and invade tissues in the urinary tract. […] The underlying host factors largely determine the pathogenesis of complicated UTIs. Impairment of the immune system and voiding dysfunction from autonomic neuropathy may predispose patients with diabetes to develop UTIs.

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

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

  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. […] Changes in this surface can cause permeability alterations that allow potassium ions to traverse the urothelium, depolarize sensory and motor nerves, and activate mast cells. This permeability dysfunction is manifested by increased urea absorption and positive potassium sensitivity tests in IC patients. […] 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. […] Substance P, a tachykinin released by activated C-fiber afferents, is involved in nociception in the central and peripheral nervous systems and also functions as an inflammatory mediator. Substance P release results in an inflammatory cascade with mast cell activation and up-regulation of adjacent nerves (sensory, autonomic, motor).

• #69 Pathomechanism of Interstitial Cystitis/Bladder Pain Syndrome and Mapping the Heterogeneity of Disease

  https://www.einj.org/journal/view.php?doi=10.5213/inj.1632712.356

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. […] It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. […] Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. […] The pathophysiology of IC/BPS might involve chronic inflammation, increased apoptosis, urothelial dysfunction, and CNS sensitization. […] Bladder urothelium denudation and thinning, aberrant synthesis of proteoglycans, cell adhesive proteins and tight junction proteins, and bacterial defence molecules were found in the IC/BPS bladders.

• #70 Chemical hemorrhagic cystitis: Diagnostic and therapeutic pitfalls (Review)

  https://www.spandidos-publications.com/10.3892/etm.2021.10056

  Chemical cystitis (CC) is an inflammation of the bladder caused by various chemical agents ingested intentionally or accidentally. […] CC is caused by different chemical agents ingested orally, intravenously, through instillation therapy, or topical contiguity. […] CC is attributed to chemotherapeutic or immunologic drug administration such as cyclophosphamide, medication administered for different pathologies, or the use of certain anesthetic drugs in a recreational manner, such as ketamine. […] CC is noninfectious cystitis, and it is caused by chemical irritation of the bladder mucosa. […] CC tends to be more aggressive than infectious cystitis, with more severe irritative lower urinary tract symptoms (LUTS), hematuria, and bladder pain. […] Cyclophosphamide is an oxazophosphorine compound, and its urinary tract toxicity is proven to be dose-related.

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

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

  PRP is rich in several kinds of growth factors that promote the resolution of inflammation and facilitate wound healing. […] Local treatment with LESWs has shown demonstrated efficacy in reducing inflammation, improving blood perfusion, and facilitating tissue regeneration. […] 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. […] Treatment of IC/BPS should distinguish between different clinical phenotypes, the underlying pathophysiology causing clinical symptoms, and visual exploration of bladder lesions.

Zobacz więcej