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__NOTOC__
The pathophysiology of Enteropathic arthropathy:<ref name="pmid3649644">{{cite journal |vauthors=Navis ES |title=Controlling violent patients before they control you. Advice on keeping your cool when your patient is losing his |journal=Nursing |volume=17 |issue=9 |pages=52–4 |date=September 1987 |pmid=3649644 |doi= |url=}}</ref><ref name="pmid3495471">{{cite journal |vauthors=Cuvelier C, Barbatis C, Mielants H, De Vos M, Roels H, Veys E |title=Histopathology of intestinal inflammation related to reactive arthritis |journal=Gut |volume=28 |issue=4 |pages=394–401 |date=April 1987 |pmid=3495471 |pmc=1432823 |doi= |url=}}</ref><ref name="pmid20485176">{{cite journal |vauthors=Jacques P, Elewaut D, Mielants H |title=Interactions between gut inflammation and arthritis/spondylitis |journal=Curr Opin Rheumatol |volume=22 |issue=4 |pages=368–74 |date=July 2010 |pmid=20485176 |doi=10.1097/BOR.0b013e3283393807 |url=}}</ref><ref name="pmid1001980">{{cite journal |vauthors=Mallas EG, Mackintosh P, Asquith P, Cooke WT |title=Histocompatibility antigens in inflammatory bowel disease. Their clinical significance and their association with arthropathy with special reference to HLA-B27 (W27) |journal=Gut |volume=17 |issue=11 |pages=906–10 |date=November 1976 |pmid=1001980 |pmc=1411211 |doi= |url=}}</ref><ref name="pmid8733445">{{cite journal |vauthors=Brown MA, Pile KD, Kennedy LG, Calin A, Darke C, Bell J, Wordsworth BP, Cornélis F |title=HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom |journal=Ann. Rheum. Dis. |volume=55 |issue=4 |pages=268–70 |date=April 1996 |pmid=8733445 |pmc=1010149 |doi= |url=}}</ref><ref name="pmid10640771">{{cite journal |vauthors=Mertz AK, Wu P, Sturniolo T, Stoll D, Rudwaleit M, Lauster R, Braun J, Sieper J |title=Multispecific CD4+ T cell response to a single 12-mer epitope of the immunodominant heat-shock protein 60 of Yersinia enterocolitica in Yersinia-triggered reactive arthritis: overlap with the B27-restricted CD8 epitope, functional properties, and epitope presentation by multiple DR alleles |journal=J. Immunol. |volume=164 |issue=3 |pages=1529–37 |date=February 2000 |pmid=10640771 |doi= |url=}}</ref><ref name="pmid19468997">{{cite journal |vauthors=Fantini MC, Pallone F, Monteleone G |title=Common immunologic mechanisms in inflammatory bowel disease and spondylarthropathies |journal=World J. Gastroenterol. |volume=15 |issue=20 |pages=2472–8 |date=May 2009 |pmid=19468997 |pmc=2686905 |doi= |url=}}</ref><ref name="pmid7964509">{{cite journal |vauthors=Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernández-Sueiro JL, Balish E, Hammer RE |title=The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats |journal=J. Exp. Med. |volume=180 |issue=6 |pages=2359–64 |date=December 1994 |pmid=7964509 |pmc=2191772 |doi= |url=}}</ref><ref name="pmid15539413">{{cite journal |vauthors=Laukens D, Peeters H, Marichal D, Vander Cruyssen B, Mielants H, Elewaut D, Demetter P, Cuvelier C, Van Den Berghe M, Rottiers P, Veys EM, Remaut E, Steidler L, De Keyser F, De Vos M |title=CARD15 gene polymorphisms in patients with spondyloarthropathies identify a specific phenotype previously related to Crohn's disease |journal=Ann. Rheum. Dis. |volume=64 |issue=6 |pages=930–5 |date=June 2005 |pmid=15539413 |pmc=1755516 |doi=10.1136/ard.2004.028837 |url=}}</ref><ref name="pmid16937463">{{cite journal |vauthors=Rothfuss KS, Stange EF, Herrlinger KR |title=Extraintestinal manifestations and complications in inflammatory bowel diseases |journal=World J. Gastroenterol. |volume=12 |issue=30 |pages=4819–31 |date=August 2006 |pmid=16937463 |pmc=4087615 |doi= |url=}}</ref>
{{Zenker's diverticulum}}
*Although the pathogenesis of EA has not been plainly clarified, the observation that joint inflammation occurs in genetically predisposed subjects with bacterial gut infections provided an important evidence for a possible relationship between inflammation of the gut mucosa and arthritis.  
{{CMG}} {{AE}}
*Current theories provide, in genetically predisposed subjects, an aberrant migration of intestinal lymphocytes or macrophages from inflamed gut mucosa to joints, in which an important role was played by gut bacteria.
 
*In fact, a dysfunctional interaction between the mucosal immune system and gut bacteria could result in an abnormal state of immunological tolerance toward flora by alterations in mucosal effector cells or by affecting regulatory cells.  
==Overview==
*A significant evidence for the pathogenic role of gut bacteria in the pathogenesis of SpA is derived from animals models.
 
*Genetic factors play a predisposing role while environmental factors, such as infectious agents, may play a causative role.
==Pathophysiology==
*Among the genetic factors, HLA-B27 has the strongest genetic association with SpA and in particular with ankylosing spondylitis (AS).  
The pathophysiology of the Zenker's diverticulum is as follows
*This association is reported in more than 90% of cases, also spondylitis in IBD is associated with the presence of HLA-B27, however, in lower frequencies than in AS (30%–80%).  
* Zenker's diverticula (ZD) is thought to be due to the result of motor abnormalities of the esophagus.
*Pure asymptomatic sacroiliitis in CD is not strongly associated with HLA-B27 and a very recent study indicates a prevalence of 7%.  
* ZD is a defect over the  Killian's triangle, a point of weakness in the muscular wall of the hypopharynx.
*In 2000, Orchard et al. described an association with HLA-DR0103, B35, and B27 in type 1 peripheral arthritis and neither B27 nor DR4 associations were observed in type 2 arthritis.
* Killian's triangle is surrounded by the cricopharyngeal sphincter and oblique fibers of the inferior constrictor of the pharyngeal muscle.
*In order to describe the role of HLA-B27 in the pathogenesis of EA, different theories have been proposed.
* ZD should be considered a pseudodiverticulum as it includes only mucosa and submucosa.
*One theory suggests that HLA-B27-expressing macrophages expose specific bacterial antigens that may activate CD4+ T-cells with their migration from gut to joint with the development of arthritis.
* Chronic strain on the Killian's triangle leads to an evagination of the sphincter, which may be because of the high pressures in the food bolus in the course of swallowing and the abnormalities of the upper esophageal sphincter (UES).
*Another theory proposes that homology between HLA-B27 sequences and bacterial antigens may activate T-cell and inflammation by antigen mimicry mechanism.  
* This failure to achieve adequate diameter for effective bolus clearance leads to a subsequent increase in the hypopharyngeal pressure gradient.
*Finally, the most recent theory is based on the endoplasmic reticulum stress: under normal conditions, the peptide-loaded HLA class I heavy chain binds the β2-microglobulin (β2m) in the endoplasmic reticulum. The folding process of the HLA-B27 heavy chain is slower than that of other HLA alleles thus leading to the generation of misfolded chains.
* Increased intrabolus pressures found in patients with ZD can be secondary to impaired bolus passage combined with the gastroesophageal reflux disease (GERD) or as a result of the GERD.
*Misfolded chains are usually removed in the endoplasmic reticulum, but in certain conditions, such as viral infection, they accumulate thus activating the protein BiP, the endoplasmic reticulum-unfolded-protein-response (UPR) and the nuclear factor κB (NFκB), which play a critical role in the induction of inflammation.
* As the diverticulum enlarges, it may compress the pharyngoesophageal segment as well as increased stiffness and the intrabolus pressure.
*Data suggest that deposition of β2m, caused by the high dissociation rate between the HLA-B27 heavy chain and β2m, occurring within synovial tissue, may lead to the initiation of chronic inflammation.
* Increased intrabolus pressure is also increased in older patients who perform multiple swallows to achieve bolus clearance.
*Other HLA genes have been associated with SpA in IBD: HLA-DrB10103, HLA-B35, HLA-B24 in type 1 peripheral arthritis, and HLA-B44 in type 2 peripheral arthritis.  
* Various hypothesis involved in the pathogenesis of the Zenker's diverticulum are as follows<ref name="pmid1397879">{{cite journal |vauthors=Cook IJ, Gabb M, Panagopoulos V, Jamieson GG, Dodds WJ, Dent J, Shearman DJ |title=Pharyngeal (Zenker's) diverticulum is a disorder of upper esophageal sphincter opening |journal=Gastroenterology |volume=103 |issue=4 |pages=1229–35 |year=1992 |pmid=1397879 |doi= |url=}}</ref><ref name="pmid1283083">{{cite journal |vauthors=Cook IJ, Blumbergs P, Cash K, Jamieson GG, Shearman DJ |title=Structural abnormalities of the cricopharyngeus muscle in patients with pharyngeal (Zenker's) diverticulum |journal=J. Gastroenterol. Hepatol. |volume=7 |issue=6 |pages=556–62 |year=1992 |pmid=1283083 |doi= |url=}}</ref><ref name="pmid1634178">{{cite journal |vauthors=Fulp SR, Castell DO |title=Manometric aspects of Zenker's diverticulum |journal=Hepatogastroenterology |volume=39 |issue=2 |pages=123–6 |year=1992 |pmid=1634178 |doi= |url=}}</ref><ref name="pmid12928096">{{cite journal |vauthors=Sasaki CT, Ross DA, Hundal J |title=Association between Zenker diverticulum and gastroesophageal reflux disease: development of a working hypothesis |journal=Am. J. Med. |volume=115 Suppl 3A |issue= |pages=169S–171S |year=2003 |pmid=12928096 |doi= |url=}}</ref><ref name="pmid7923848">{{cite journal |vauthors=Resouly A, Braat J, Jackson A, Evans H |title=Pharyngeal pouch: link with reflux and oesophageal dysmotility |journal=Clin Otolaryngol Allied Sci |volume=19 |issue=3 |pages=241–2 |year=1994 |pmid=7923848 |doi= |url=}}</ref><ref name="pmid11715923">{{cite journal |vauthors=Mulder CJ, Costamagna G, Sakai P |title=Zenker's diverticulum: treatment using a flexible endoscope |journal=Endoscopy |volume=33 |issue=11 |pages=991–7 |year=2001 |pmid=11715923 |doi=10.1055/s-2004-826106 |url=}}</ref><ref name="pmid5428852">{{cite journal |vauthors=Hunt PS, Connell AM, Smiley TB |title=The cricopharyngeal sphincter in gastric reflux |journal=Gut |volume=11 |issue=4 |pages=303–6 |year=1970 |pmid=5428852 |pmc=1411416 |doi= |url=}}</ref>
*Moreover, Mielants et al. showed an association between HLA-Bw62 and chronic gut lesions associated with a family history of AS and CD, with markers of inflammation, reduced axial mobility, the presence of sacroiliitis, destructive joint lesions, and a diagnosis of AS.
# Zenker's diverticulum is a disorder of diminished upper esophageal sphincter, incomplete sphincter opening is probably the cause of dysphagia. Increased hypopharyngeal pressures throughout swallowing are probably important in the pathogenesis of the diverticulum.
*Further confirming the relevance of HLA-B27 in the pathogenesis of enteroarthritis, Hammer et al. studied transgenic rats overexpressing HLA-B27 molecule. These rats developed a multisystemic inflammatory disease that had several clinical and histopathological similarities to SpA and IBD [54]. An important finding was that these rats did not develop joint or gut inflammation when they were in a germ-free environment [55]. This result supports the theory of the participation of microorganisms in the pathogenesis of these diseases.
# The nemaline bodies and red ragged fibers are usually the normal cricopharyngeous findings. whereas the Zenker's diverticulum is characterized by adipose tissue deposition and degeneration of the fiber these structural modifications can impair the UES opening and dysphagia ensues.
*In humans with reactive arthritis, following Yersinia enterocolitica, Shigella spp. or Salmonella enteritidis and Typhimurium infection, bacterial antigens have been detected in joints [56–59]. Later studies further confirmed this evidence.
# Nineteen patients in the sample were found to have reflux and 20 had dysmotility. These findings suggest that pharyngeal pouches are not a purely localized incoordination of the cricopharyngeal sphincter but are associated with a generalized oesophageal muscle dysfunction.
*Other molecular studies found similarities between Klebsiella nitrogenase and HLA-B27 and between Klebsiella pullulanase and collagen fibers types I, III, and IV.
# Acid reflux induces longitudinal esophageal shortening, which in turn increases the chance for the development of herniation between two spatially associated structures, the pharyngeal constrictors and cricopharyngeus muscles, leading to the development of Zenker diverticulum
*Interestingly, elevated levels of antibodies against Klebsiella and collagen fibers types I, III, IV, and V were detected in patients with CD and AS.
# Zenker's diverticulum is thought to result from disordered coordination among the pharynx and upper esophageal sphincter.  
*In addition to HLA-B27, other genes have been identified as being related to SpA and IBD. In fact, several common genetic predispositions between SpA and IBD were identified, of which the association with IL-23R polymorphisms is most prominent.  
#* Manometric studies of the upper esophagus were used in testing the hypothesis of dysmotility in the formation and growth of a Zenker's diverticulum; however, the data have provided conflicting evidence.  
*The functional role of IL-23 receptor polymorphisms remains unclear, the fact that IL-23 signaling plays a critical role in the Th17-mediated inflammation indicates that Th17 cells may represent a common pathogenetic mechanism in both IBD and SpA.  
#* Manometric studies show that resting upper esophageal sphincter strain is normal in some patients with Zenker's diverticulum and decreased in others. abnormal premature relaxation and contraction of the upper esophageal sphincter seen in some patients with Zenker's diverticulum may be accompanied with the aid of pharyngeal contractions against a closed sphincter.  
*The first susceptibility gene that has been identified for CD is CARD15 (or NOD2). Variants within this gene increase the risk for CD by threefold for heterozygous and fortyfold for homozygous individuals.  
#* This abnormality is thought by a few investigators to be the cause of Zenker's diverticulum, but not by others who have found normal upper sphincter relaxation.
*An association was also found in SpA patients between the carriage of CARD15 variants and the development of chronic subclinical gut inflammation.  
# In summary, in-coordination of pharyngeal contraction and UES opening has also been variably demonstrated by some investigator.
*Although CARD15 mutations do not seem to predispose to arthritis, it might confer a risk towards the development of (sub) clinical gut inflammation in SpA patients, rendering these patients more disposed to develop IBD.
* All the above-mentioned hypotheses lead to herniation within the Killian's triangle, inclusive of disorders associated with altered UES function, unusual esophageal motility, esophageal shortening.
*A CARD15-mediated NFκB-dependent inflammatory reaction might be an important pathogenic process within the joints.
* This leads to the creation of a sac with a narrow neck that can trap liquid and food, the distended sac may compress the cervical esophagus.
*The protein is expressed in the joint tissue, and bacterial cell wall components have been demonstrated in the synovium of SpA patients, supporting the idea that CARD15 can locally trigger inflammation.
* Impaired bolus passage leads to increases intrabolus pressure which leads to herniation in the Killians triangle.
*Recently, additionally shared associations between SpA and IBD were found at chromosome 1q32 near KIF21B (genome-wide significant), STAT3, IL-12B, CDKAL1, LRRK2/MUC19, and chromosome 13q14 (experiment-wise association).  
* Acid reflux is thought to lead to increased spasm of the UES which in turn increases the intrabolus pressures during swallowing, given that swallowing is frequently distinct from episodes of acid reflux disease.
*As the genes IL-23R, STAT3, and IL-12B all influence Th17 lymphocyte differentiation/activation, this provides further evidence implicating the Th17 lymphocyte subset in the pathogenesis of SpA.
 
*In addition to genetic susceptibility, an important role was also been given to the environmental factors in triggering the onset of disease.
=== Histopathological Findings: Zenker's diverticulum ===
*In fact, bacterial gut infections such as Yersinia enterocolitica, Salmonella typhimurium, Campylobacter jejuni, and Shigella spp may cause joint inflammation in genetically predisposed patients.  
{{#ev:youtube|CEYU0Dq9n2s}}
*Given the prototypical link between certain bacterial infections and the onset of reactive arthritis, several studies have aimed to assess the role of intestinal flora in disease progression, as well as the resulting changes in mucosal response.  
 
*On the basis of these observations, the possible pathways involved in joint and gut inflammation in EA may be the following: in the acute phase of inflammation, bacterial infections can cause acute intestinal inflammation.
==References==
*Certain bacteria may survive intracellularly in macrophages that can traffic to the joint and cause arthritis in a genetically predisposed host. *Proinflammatory cytokines such as TNF and IL-23 are produced locally, with Paneth cells being the most important producers of IL-23 in the intestine.
{{reflist|2}}
*This expression can activate innate immune cells (NK) to produce IL-22 that may help control inflammation at mucosal sites.
 
*Otherwise, damage and pathogen-associated molecular pattern molecules (DAMPs and PAMPs) and cellular stretch might promote initiation of joint inflammation.
==Classification==
*In the transition phase, acute intestinal and articular inflammation can be sustained due to defective immune regulation by TREG cells, or by ER stress, whereas iNKT cells act as regulators to control inflammation. Proangiogenic factors such as PlGF can lead to aberrant neovascularisation. *These events may lead to chronicity, further enhanced or maintained by repetitive cellular stress.  
Esophageal diverticula are classified on the basis of  location into three types
*In this stage, stromal cells become more important, as targets for proinflammatory cytokines
 
*
1. Phrenoesophageal (Zenker's diverticulum-70%),
*
 
*
2. Epiphrenic (20%) 
*
 
3. Thoracic and mediastinal (10%) 
 
Almost all esophageal diverticula are acquired pulsion diverticula.  
 
 
==Clinical examination==
[[Asymptomatic]] in patients with small [[Zenker's diverticulum|Zenker's]] [[diverticulum]], the severity of the symptoms is proportional to the size of the diverticulum.<ref name="urlZenkers diverticulum: exploring treatment options">{{cite web |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773964/ |title=Zenker's diverticulum: exploring treatment options |format= |work= |accessdate=}}</ref><ref name="urlZenkers diverticula: pathophysiology, clinical presentation, and flexible endoscopic management. - PubMed - NCBI">{{cite web |url=https://www.ncbi.nlm.nih.gov/pubmed/18197932 |title=Zenker's diverticula: pathophysiology, clinical presentation, and flexible endoscopic management. - PubMed - NCBI |format= |work= |accessdate=}}</ref><ref name="urlZenkers Diverticulum. - PubMed - NCBI">{{cite web |url=https://www.ncbi.nlm.nih.gov/pubmed/24055983 |title=Zenker's Diverticulum. - PubMed - NCBI |format= |work= |accessdate=}}</ref><ref name="url[Hypopharyngeal Zenkers diverticulum as a clinical and surgical problem]. - PubMed - NCBI">{{cite web |url=https://www.ncbi.nlm.nih.gov/pubmed/16989439 |title=[Hypopharyngeal Zenker's diverticulum as a clinical and surgical problem]. - PubMed - NCBI |format= |work= |accessdate=}}</ref><ref name="urlSimultaneously occurring Zenkers diverticulum and Killian-Jamieson diverticulum: case report and literature review. - PubMed - NCBI">{{cite web |url=https://www.ncbi.nlm.nih.gov/pubmed/28625183 |title=Simultaneously occurring Zenker's diverticulum and Killian-Jamieson diverticulum: case report and literature review. - PubMed - NCBI |format= |work= |accessdate=}}</ref><ref name="pmid18197932">{{cite journal |vauthors=Ferreira LE, Simmons DT, Baron TH |title=Zenker's diverticula: pathophysiology, clinical presentation, and flexible endoscopic management |journal=Dis. Esophagus |volume=21 |issue=1 |pages=1–8 |year=2008 |pmid=18197932 |doi=10.1111/j.1442-2050.2007.00795.x |url=}}</ref>
 
'''Common symptoms'''
 
[[Dysphagia]]
 
Local pain
 
Food [[regurgitation]]
 
[[Halitosis]]
 
[[Coughing]]
 
[[Hoarseness]]
 
[[Aspiration pneumonia]]
 
[[Bronchitis]]
 
'''Less common symptoms'''
 
[[Pill (pharmacology)|Pill]] [[dysphagia]]- pills stuck in the throat
 
[[Drooling]] of the [[saliva]]
 
[[Choking]] on the food
 
[[Globus sensation]]
 
Weight loss
 
[[Cervical]] [[borborgymi]]
 
[[Hemoptysis]]
 
[[Hematemesis]]
 
==Natural history==
Zenker’s diverticulum presents as a progressive dysphagia. Initially, the patient presents with
minor throat irritation, foreign body sensation, and coughing.
Symptoms worsen as the diverticulum enlarges, and pouch becomes large enough to contain food, sputum or even medications. Patients can complain of food regurgitation several hours after a meal and typically describe weight loss.
Cachexia and malnutrition can develop with Zenker’s Diverticulum, particularly in the elderly who develop a “fear of
eating” secondary to choking spells.
==Links==
https://throatdisorder.com/zenkers-diverticulum/
 
[[Category:Gastroenterology]]
[[Category:Otolaryngology]]
[[Category:Needs patient information]]
[[Category:Disease]]
<references />
 
 
==Surgery==
==Surgery==
 
=Indications=
* The indications of the surgery are as follows<ref name="urlPrinciples of surgical treatment of Zenker diverticulum">{{cite web |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307087/ |title=Principles of surgical treatment of Zenker diverticulum |format= |work= |accessdate=}}</ref>
* Severe dysphagia
* Weight loss
* Age- Elderly
* 
 
=Procedure=
*The steps of the procedure is as follows<ref name="urlZenkers Diverticulum: Carbon Dioxide Laser Endoscopic Surgery">{{cite web |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963375/ |title=Zenker's Diverticulum: Carbon Dioxide Laser Endoscopic Surgery |format= |work= |accessdate=}}</ref>
*The surgery is done under general anesthesia.
*Classic rigid oesophagoscopy was performed to prove the typical location of the diverticular inlet at the posterior wall of the hypopharynx,
*Diverticular inlet is cleared for any food debris and the meticulous search for the cancerous growths should be done.
*The diverticular sac is exposed using a Weerda distending diverticuloscope.
*The anterior lip of the diverticuloscope is placed into the esophagus while the posterior lip of the diverticuloscope is passed into the diverticulum.
*The diverticuloscope is advanced to the bottom of the diverticulum.
*The tissue bridge between the esophagus anteriorly and the diverticulum posteriorly is set between the two lips of the diverticuloscope.
*An operating microscope Carl Zeiss OPMI Sensera with attached carbon dioxide laser micromanipulator is set on working distance 400 mm with the laser beam focused on the tissue bridge.
*Carbon dioxide laser Lumenis AcuPulse with super-pulse delivery in a repeat mode, coupled with an AcuSpot micromanipulator, until 2009. Since March 2010, a robotic digital AcuBlade scanning micromanipulator system was used.
*The esophageal mucosa is protected from accidental laser injury by a moist swab.
*Using the laser at 5–10 W, the septum is transected at the midline down to the bottom of the diverticular sac. Occasionally electrocautery was used to control bleeding. * A feeding tube was introduced in all patients.
*Postoperative oesophagogram is performed at 5-6th day followed by a removal of the feeding tube and the discharge from the hospital on the same day or the day after.
*Antibiotic treatment with cefuroxime is routinely administered for one week following the surgery to prevent the post-operative infection.
*Control contrast esophagogram and subjective evaluation of swallowing were performed at least three months after the treatment
=Complications=
*Fistula
*Post operative [[hematoma]]
*Mediastinitis
*Neck emphysema
*Mucosal perforation or tearing
*Tooth fracture
*Postoperative bleeding 
*Aspiration pneumonia
*Transient left recurrent laryngeal nerve paralysis
*Edema of the laryngeal inlet and left pyriform sinus
<references />
 
==Causes==
*Zenker's diverticulum also known as pharyngosophageal diverticulum.
*It is an acquired sac-like outpouching of the mucosa and submucosa layers originating from the pharyngoesophageal junction.
*Since it involves only the mucosa and submucosa it is a false diverticulum.
*Killian's dehiscence- pulsion false diverticulum occurring dorsally at the pharyngoesophageal wall bounded by the propulsive oblique inferior pharyngeal constrictor muscle and the transversal fibers of the cricopharyngeal muscle 
*ZD occurs due to increased intraluminal pressure in the oropharynx during swallowing, against an inadequate relaxation of the cricopharyngeal muscle, and subsequent incomplete opening of the UES, causing the protrusion of the mucosa through an area of relative weakness at the dorsal pharyngoesophageal wall.
 
 
==Historical Perspective==
The history of the ZD is as follows:<ref name="urlZenkers diverticulum: exploring treatment options">{{cite web |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773964/ |title=Zenker's diverticulum: exploring treatment options |format= |work= |accessdate=}}</ref><ref name="urlZenkers diverticulum: exploring treatment options2">{{cite web |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773964/ |title=Zenker's diverticulum: exploring treatment options |format= |work= |accessdate=}}</ref><ref name="urlwww.annalsthoracicsurgery.org">{{cite web |url=http://www.annalsthoracicsurgery.org/article/0003-4975(91)90153-H/pdf |title=www.annalsthoracicsurgery.org |format= |work= |accessdate=}}</ref><ref name="urlEndoscopic treatment of Zenkers diverticulum - Gastrointestinal Endoscopy">{{cite web |url=http://www.giejournal.org/article/S0016-5107(99)70452-9/pdf |title=Endoscopic treatment of Zenker's diverticulum - Gastrointestinal Endoscopy |format= |work= |accessdate=}}</ref><ref>Ludlow A. A case of obstructed deglutition, from a preternatural dilatation of, and bag formed in, the pharynx. Med Observations and Inquiries 1767;3:85-101</ref><ref>Bell C. Surgical observations. London: Longmans, Greene
and Co, 1816:6470</ref><ref>Rokitansky C. Divertikel am Pharynx. Jahrb Dkk Osterr
Staates 1840;30:222-5</ref><ref>Zenker FA, von Ziemssen H. Krankheiten des Oesophagus.
In: von Ziemssen H, ed. Handbuch der Speaellen Pathologie
und Therapie, vol 7 (suppl). Leipzig: FC Vogel, 18rn1-87</ref><ref>Killian G. La boudre de I’oesophage. Ann Ma1 Orielle Larynx
1908;Xl</ref><ref>Bensaude R, Gregoire R, Guenaux G. Diagnostic et traitement
des diverticules oesophagiens. Arch Ma1 App Digest
1922; 12: 145-203</ref><ref>Bell C. Cited by Bensaude R, Gregoire R, Guenaux G.
Diagnostic et traitement des diverticules oesophagiens. Arch
Ma1 App Digest 1922;12:145-203</ref><ref>Nicoladoni K. Behandlung der Oesophagusdivertikel. Wien
Med Wochenschr 1877;25:606-607</ref><ref>Kluge. Cited by Konig F. Die Krankheiten des unteren
Theiles des Pharynx und des Oesophagus. Deutsche Chir
1880;35:94</ref><ref> Niehans. Cited by Girard C. Du traitement des diverticules
de Yoesophage. Congres Franc Chir 1896;10:392407</ref><ref>Wheeler WI. Pharyngocele and dilatation of pharynx, with
existing diverticulum at lower portion of pharynx lying
posterior to the oesophagus, cured by pharyngotomy, being
the first case of the kind recorded. Dublin J Med Sci 1886;82
349-57</ref><ref>Von Bergmann E. Ueber den Oesophagusdivertikel und
seine Behandlung. Arch Klin Chir 1892;43:1-30</ref><ref>Kocher T. Das Oesophagusdivertikel und dessen Behandlung.
Correspondblatt Schweiz Aerzte 1892;22:23?-44</ref><ref>Butlin HF. On the removal of a pressure pouch of the
oesophagus. Med Chir Trans 1893;76:269-78</ref><ref>Schwarzenbach E. Zur operativen Behandlung und Aetiologie
der Oesophagusdivertikel. Wien Klin Wochenschr 1893;
6:43540, 453-5, 474-6</ref>     
*It was named in 1877 by German [[pathologist]] [[Friedrich Albert von Zenker]].
*The first description of Zenker's diverticulum dates back to 1769 by Ludlow
*A century later, a German pathologist, Friedrich Albert von Zenker, recognized and further characterized the physiopathology of this diverticulum.
*In 1877 Zenker and Ziemssen reviwed the world literature on the Zenker's diverticulum.
*In 1840 Rokitansky first described traction diverticula of the thoracic esophagus.
*Until 1816 publication,ZD was thought to be congenital or traumatic in origin.  
*In 1877, von Zeimssen, Professor in Munich, published "Krankheiten des Oesophagus" on the esophageal ulceration and  diverticula.
*Preliminary thoughts on managing pharyngoesophageal diverticula originated as early as 1830, when Bell proposed the establishment of a fistula to empty the diverticulum of its contents.
*The first recorded practice of this was by Nicoladoni in Vienna in 1877.
*An unsuccessful attempt at excision of the diverticulum, first suggested by Kluge in 1850, was performed in 1884 by Niehans.
*The first successful resection was by Wheeler in 1885, followed by additional favorable reports of von Bergmann and Kocher in 1892 and Butlin and Billroth in 1893.
*In 1896 Girard devised a method of invaginating the diverticulum into the esophagus, oversewing the resultant dimple.
*In some cases this procedure led to very satisfactory results, although at least one complete recurrence was documented by Waggett and Davis [17] in a patient after a fit of violent sneezing.
*Diverticulopexy was also described in this early period by Schmid, and was first performed by Hill in 1917.
*In 1910 that Stetton was able to publish a list of all cases operated on up to that time organized according to surgical technique.
*These methods included primary excision, excision after preliminary gastrostomy, invagination of the sac, mucosal destruction without excision, and two-stage excision.
http://www.annalsthoracicsurgery.org/article/0003-4975(91)90153
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Latest revision as of 19:12, 11 April 2018

The pathophysiology of Enteropathic arthropathy:[1][2][3][4][5][6][7][8][9][10]

  • Although the pathogenesis of EA has not been plainly clarified, the observation that joint inflammation occurs in genetically predisposed subjects with bacterial gut infections provided an important evidence for a possible relationship between inflammation of the gut mucosa and arthritis.
  • Current theories provide, in genetically predisposed subjects, an aberrant migration of intestinal lymphocytes or macrophages from inflamed gut mucosa to joints, in which an important role was played by gut bacteria.
  • In fact, a dysfunctional interaction between the mucosal immune system and gut bacteria could result in an abnormal state of immunological tolerance toward flora by alterations in mucosal effector cells or by affecting regulatory cells.
  • A significant evidence for the pathogenic role of gut bacteria in the pathogenesis of SpA is derived from animals models.
  • Genetic factors play a predisposing role while environmental factors, such as infectious agents, may play a causative role.
  • Among the genetic factors, HLA-B27 has the strongest genetic association with SpA and in particular with ankylosing spondylitis (AS).
  • This association is reported in more than 90% of cases, also spondylitis in IBD is associated with the presence of HLA-B27, however, in lower frequencies than in AS (30%–80%).
  • Pure asymptomatic sacroiliitis in CD is not strongly associated with HLA-B27 and a very recent study indicates a prevalence of 7%.
  • In 2000, Orchard et al. described an association with HLA-DR0103, B35, and B27 in type 1 peripheral arthritis and neither B27 nor DR4 associations were observed in type 2 arthritis.
  • In order to describe the role of HLA-B27 in the pathogenesis of EA, different theories have been proposed.
  • One theory suggests that HLA-B27-expressing macrophages expose specific bacterial antigens that may activate CD4+ T-cells with their migration from gut to joint with the development of arthritis.
  • Another theory proposes that homology between HLA-B27 sequences and bacterial antigens may activate T-cell and inflammation by antigen mimicry mechanism.
  • Finally, the most recent theory is based on the endoplasmic reticulum stress: under normal conditions, the peptide-loaded HLA class I heavy chain binds the β2-microglobulin (β2m) in the endoplasmic reticulum. The folding process of the HLA-B27 heavy chain is slower than that of other HLA alleles thus leading to the generation of misfolded chains.
  • Misfolded chains are usually removed in the endoplasmic reticulum, but in certain conditions, such as viral infection, they accumulate thus activating the protein BiP, the endoplasmic reticulum-unfolded-protein-response (UPR) and the nuclear factor κB (NFκB), which play a critical role in the induction of inflammation.
  • Data suggest that deposition of β2m, caused by the high dissociation rate between the HLA-B27 heavy chain and β2m, occurring within synovial tissue, may lead to the initiation of chronic inflammation.
  • Other HLA genes have been associated with SpA in IBD: HLA-DrB10103, HLA-B35, HLA-B24 in type 1 peripheral arthritis, and HLA-B44 in type 2 peripheral arthritis.
  • Moreover, Mielants et al. showed an association between HLA-Bw62 and chronic gut lesions associated with a family history of AS and CD, with markers of inflammation, reduced axial mobility, the presence of sacroiliitis, destructive joint lesions, and a diagnosis of AS.
  • Further confirming the relevance of HLA-B27 in the pathogenesis of enteroarthritis, Hammer et al. studied transgenic rats overexpressing HLA-B27 molecule. These rats developed a multisystemic inflammatory disease that had several clinical and histopathological similarities to SpA and IBD [54]. An important finding was that these rats did not develop joint or gut inflammation when they were in a germ-free environment [55]. This result supports the theory of the participation of microorganisms in the pathogenesis of these diseases.
  • In humans with reactive arthritis, following Yersinia enterocolitica, Shigella spp. or Salmonella enteritidis and Typhimurium infection, bacterial antigens have been detected in joints [56–59]. Later studies further confirmed this evidence.
  • Other molecular studies found similarities between Klebsiella nitrogenase and HLA-B27 and between Klebsiella pullulanase and collagen fibers types I, III, and IV.
  • Interestingly, elevated levels of antibodies against Klebsiella and collagen fibers types I, III, IV, and V were detected in patients with CD and AS.
  • In addition to HLA-B27, other genes have been identified as being related to SpA and IBD. In fact, several common genetic predispositions between SpA and IBD were identified, of which the association with IL-23R polymorphisms is most prominent.
  • The functional role of IL-23 receptor polymorphisms remains unclear, the fact that IL-23 signaling plays a critical role in the Th17-mediated inflammation indicates that Th17 cells may represent a common pathogenetic mechanism in both IBD and SpA.
  • The first susceptibility gene that has been identified for CD is CARD15 (or NOD2). Variants within this gene increase the risk for CD by threefold for heterozygous and fortyfold for homozygous individuals.
  • An association was also found in SpA patients between the carriage of CARD15 variants and the development of chronic subclinical gut inflammation.
  • Although CARD15 mutations do not seem to predispose to arthritis, it might confer a risk towards the development of (sub) clinical gut inflammation in SpA patients, rendering these patients more disposed to develop IBD.
  • A CARD15-mediated NFκB-dependent inflammatory reaction might be an important pathogenic process within the joints.
  • The protein is expressed in the joint tissue, and bacterial cell wall components have been demonstrated in the synovium of SpA patients, supporting the idea that CARD15 can locally trigger inflammation.
  • Recently, additionally shared associations between SpA and IBD were found at chromosome 1q32 near KIF21B (genome-wide significant), STAT3, IL-12B, CDKAL1, LRRK2/MUC19, and chromosome 13q14 (experiment-wise association).
  • As the genes IL-23R, STAT3, and IL-12B all influence Th17 lymphocyte differentiation/activation, this provides further evidence implicating the Th17 lymphocyte subset in the pathogenesis of SpA.
  • In addition to genetic susceptibility, an important role was also been given to the environmental factors in triggering the onset of disease.
  • In fact, bacterial gut infections such as Yersinia enterocolitica, Salmonella typhimurium, Campylobacter jejuni, and Shigella spp may cause joint inflammation in genetically predisposed patients.
  • Given the prototypical link between certain bacterial infections and the onset of reactive arthritis, several studies have aimed to assess the role of intestinal flora in disease progression, as well as the resulting changes in mucosal response.
  • On the basis of these observations, the possible pathways involved in joint and gut inflammation in EA may be the following: in the acute phase of inflammation, bacterial infections can cause acute intestinal inflammation.
  • Certain bacteria may survive intracellularly in macrophages that can traffic to the joint and cause arthritis in a genetically predisposed host. *Proinflammatory cytokines such as TNF and IL-23 are produced locally, with Paneth cells being the most important producers of IL-23 in the intestine.
  • This expression can activate innate immune cells (NK) to produce IL-22 that may help control inflammation at mucosal sites.
  • Otherwise, damage and pathogen-associated molecular pattern molecules (DAMPs and PAMPs) and cellular stretch might promote initiation of joint inflammation.
  • In the transition phase, acute intestinal and articular inflammation can be sustained due to defective immune regulation by TREG cells, or by ER stress, whereas iNKT cells act as regulators to control inflammation. Proangiogenic factors such as PlGF can lead to aberrant neovascularisation. *These events may lead to chronicity, further enhanced or maintained by repetitive cellular stress.
  • In this stage, stromal cells become more important, as targets for proinflammatory cytokines
  1. ↑ Navis ES (September 1987). "Controlling violent patients before they control you. Advice on keeping your cool when your patient is losing his". Nursing. 17 (9): 52–4. PMID 3649644.
  2. ↑ Cuvelier C, Barbatis C, Mielants H, De Vos M, Roels H, Veys E (April 1987). "Histopathology of intestinal inflammation related to reactive arthritis". Gut. 28 (4): 394–401. PMC 1432823. PMID 3495471.
  3. ↑ Jacques P, Elewaut D, Mielants H (July 2010). "Interactions between gut inflammation and arthritis/spondylitis". Curr Opin Rheumatol. 22 (4): 368–74. doi:10.1097/BOR.0b013e3283393807. PMID 20485176.
  4. ↑ Mallas EG, Mackintosh P, Asquith P, Cooke WT (November 1976). "Histocompatibility antigens in inflammatory bowel disease. Their clinical significance and their association with arthropathy with special reference to HLA-B27 (W27)". Gut. 17 (11): 906–10. PMC 1411211. PMID 1001980.
  5. ↑ Brown MA, Pile KD, Kennedy LG, Calin A, Darke C, Bell J, Wordsworth BP, Cornélis F (April 1996). "HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom". Ann. Rheum. Dis. 55 (4): 268–70. PMC 1010149. PMID 8733445.
  6. ↑ Mertz AK, Wu P, Sturniolo T, Stoll D, Rudwaleit M, Lauster R, Braun J, Sieper J (February 2000). "Multispecific CD4+ T cell response to a single 12-mer epitope of the immunodominant heat-shock protein 60 of Yersinia enterocolitica in Yersinia-triggered reactive arthritis: overlap with the B27-restricted CD8 epitope, functional properties, and epitope presentation by multiple DR alleles". J. Immunol. 164 (3): 1529–37. PMID 10640771.
  7. ↑ Fantini MC, Pallone F, Monteleone G (May 2009). "Common immunologic mechanisms in inflammatory bowel disease and spondylarthropathies". World J. Gastroenterol. 15 (20): 2472–8. PMC 2686905. PMID 19468997.
  8. ↑ Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernández-Sueiro JL, Balish E, Hammer RE (December 1994). "The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats". J. Exp. Med. 180 (6): 2359–64. PMC 2191772. PMID 7964509.
  9. ↑ Laukens D, Peeters H, Marichal D, Vander Cruyssen B, Mielants H, Elewaut D, Demetter P, Cuvelier C, Van Den Berghe M, Rottiers P, Veys EM, Remaut E, Steidler L, De Keyser F, De Vos M (June 2005). "CARD15 gene polymorphisms in patients with spondyloarthropathies identify a specific phenotype previously related to Crohn's disease". Ann. Rheum. Dis. 64 (6): 930–5. doi:10.1136/ard.2004.028837. PMC 1755516. PMID 15539413.
  10. ↑ Rothfuss KS, Stange EF, Herrlinger KR (August 2006). "Extraintestinal manifestations and complications in inflammatory bowel diseases". World J. Gastroenterol. 12 (30): 4819–31. PMC 4087615. PMID 16937463.
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