View source for Transitional epithelium

{{Short description|A type of tissue}}
{{Infobox cell
| Name        = Transitional epithelium
| Image       = Transitional striated epith.jpg
| Caption     = Transitional epithelium
| Image2      = Harnblase Urothel.png
| Caption2    = Transitional epithelium of the [[bladder]], known as urothelium. The rounded surface of the apical cells is a distinguishing characteristic of this type of epithelium.
| Latin       =
| System      = [[Urinary system]]
}}
{{Epithelia series}}
[[File:Transitional epithelium animated.gif|alt=transitional epithelium|thumb|Transitional epithelium animation, highlighting the epithelial layer, then underlying connective tissue. Contrast the messy appearance of the epithelial surface to other epithelial tissues.]]
'''Transitional epithelium''' is a type of [[Epithelium#Stratified epithelium|stratified epithelium]].<ref name=":0">{{Cite web|last=Sapkota|first=Anupama|date=2020-09-28|title=Transitional epithelium- definition, structure, functions, examples|url=https://microbenotes.com/transitional-epithelium/|access-date=2021-10-17|website=Microbe Notes|language=en-US}}</ref> Transitional epithelium is a type of tissue that changes shape in response to stretching (stretchable epithelium). The transitional epithelium usually appears cuboidal when relaxed and squamous when stretched.<ref name=":0" /> This tissue consists of multiple layers of [[epithelial]] cells which can contract and expand in order to adapt to the degree of distension needed. Transitional epithelium lines the organs of the [[urinary system]] and is known here as '''urothelium''' ({{plural form}}: '''urothelia'''). The [[bladder]], for example, has a need for great distension.

==Structure==
The appearance of transitional epithelium differs according to its cell layer. Cells of the basal layer are [[cuboidal]] (cube-shaped), or [[columnar]] (column-shaped), while the cells of the superficial layer vary in appearance depending on the degree of distension.<ref>Marieb, E., & Hoehn, K. (2013). ''Human anatomy & physiology'' (9th ed., pp. 122-124). Boston: Pearson.</ref> These cells appear to be cuboidal with a domed apex when the organ or the tube in which they reside is not stretched. When the organ or tube is stretched (such as when the bladder is filled with urine), the tissue compresses and the cells become stretched. When this happens, the cells flatten, and they appear to be [[squamous]] and irregular.

===Cell layers===
Transitional epithelium is made up of three types of cell layers: basal, intermediate, and superficial.<ref name="Structure">Monis, B., & Zambrano, D. (1968). Ultrastructure of transitional epithelium of man. Zeitschrift für Zellforschung und Microscopical Anatomie, 87(1), 101-117.</ref> The basal layer fosters the epithelial stem cells in order to provide constant renewal of the epithelium.<ref name="Osborn">Osborn, S. L., & Kurzrock, E. A. (2015). Production of Urothelium from Pluripotent Stem Cells for Regenerative Applications. Current Urology Reports, 16(1), 1+. Retrieved from http://go.galegroup.com/ps/i.do?id=GALE%7CA390522720&v=2.1&u=clemsonu_main&it=r&p=AONE&sw=w&asid=bf6961c15c9b9523113dee93fd8df89c</ref> These cells' cytoplasm is rich in tonofilaments and [[mitochondria]]; however, they contain few [[rough endoplasmic reticulum]]. The tonofilaments play a role in the attachment of the basal layer to the basement membrane via [[desmosomes]].<ref name="Hicks-1965" /> The intermediate cell layer is highly proliferative and, therefore, provides for rapid cell regeneration in response to injury or infection of the organ or tube in which it resides.<ref name="Osborn" /> These cells contain a prominent [[Golgi apparatus]] and an array of membrane-bound vesicles.<ref name="Hicks-1965" /> These function in the packaging and transport of proteins, such as keratin, to the superficial cell layer. The cells of the superficial cell layer that lines the lumen are known as [[facet cell]]s or ''umbrella cells''. This layer is the only fully differentiated layer of the epithelium. It provides an impenetrable barrier between the lumen and the bloodstream, so as not to allow the bloodstream to reabsorb harmful wastes or pathogens.<ref name="Osborn" /> All transitional epithelial cells are covered in [[microvilli]] and a fibrillar mucous coat.<ref name="Structure" />

The epithelium contains many intimate and delicate connections to neural and connective tissue. These connections allow for communication to tell the cells to expand or contract. The superficial layer of transitional epithelium is connected to the basal layer via cellular projections, such as intermediate filaments protruding from the cellular membrane. These structural elements cause the epithelium to allow distension; however, these also cause the tissue to be relatively fragile and, therefore, difficult to study.  All cells touch the basement membrane.{{citation needed|date=March 2019}}

===Cell membrane===
The urothelium is the most impermeable membrane in the mammalian body.<ref>{{Cite journal|last1=Meldolesi|first1=J.|last2=Markham|first2=Roy|last3=Horne|first3=R. W.|last4=Hicks|first4=R. Marian|date=1974-07-04|title=Membranes and membrane surfaces: Dynamics of cytoplasmic membranes in pancreatic acinar cells|url=https://royalsocietypublishing.org/doi/10.1098/rstb.1974.0014|journal=Philosophical Transactions of the Royal Society of London. B, Biological Sciences|volume=268|issue=891|pages=39–53|doi=10.1098/rstb.1974.0014|pmid=4155089|url-access=subscription}}</ref> Because of its importance in acting as an osmotic barrier between the contents of the urinary tract and the surrounding organs and tissues, transitional epithelium is relatively impermeable to water and salts. This impermeability is due to a highly keratinized cellular membrane synthesized in the Golgi apparatus.<ref>Hicks, R. (1966). THE FUNCTION OF THE GOLGI COMPLEX IN TRANSITIONAL EPITHELIUM: Synthesis of the Thick Cell Membrane. ''The Journal of Cell Biology,'' ''30''(3), 623-643. Retrieved November 25, 2014, from http://jcb.rupress.org/content/30/3/623.abstract</ref> The membrane is made up of a hexagonal lattice put together in the Golgi apparatus and implanted into the surface of the cell by reverse pinocytosis, a type of exocytosis.<ref name="Firth">Firth, J. A., & Hicks, R. M. (1973). Interspecies variation in the fine structure and enzyme cytochemistry of mammalian transitional epithelium. Journal of Anatomy, 116(Pt 1), 31–43.</ref> The cells in the superficial layer of the transitional epithelium are highly differentiated, allowing for maintenance of this barrier membrane.<ref name="Firth" /> The basal layer of the epithelium is much less differentiated; however, it does act as a replacement source for more superficial layer.<ref name="Firth" /> While the Golgi complex is much less prominent in the cells of the basal layer, these cells are rich in cytoplasmic proteins that bundle together to form [[tonofibrils]]. These tonofibrils converge at [[hemidesmosomes]] to attach the cells at the basement membrane.<ref name="Hicks-1965">Hicks, R. (1965). The Fine Structure Of The Transitional Epithelium Of Rat Ureter. ''The Journal of Cell Biology,'' ''26''(1), 25-48. Retrieved November 25, 2014, from http://jcb.rupress.org/content/26/1/25.abstract</ref>

==Function==
The transitional epithelium cells stretch readily in order to accommodate fluctuation of volume of the liquid in an organ (the distal part of the urethra becomes non-keratinized stratified squamous epithelium in females; the part that lines the bottom of the tissue is called the [[basement membrane]]). Transitional epithelium also functions as a barrier between the [[Lumen (anatomy)|lumen]], or inside hollow space of the tract that it lines and the bloodstream. To help achieve this, the cells of transitional epithelium are connected by tight junctions, or virtually impenetrable junctions that seal together to the cellular membranes of neighboring cells. This barrier prevents re-absorption of toxic wastes and pathogens by the bloodstream. 

==Clinical significance==
Urothelium is susceptible to carcinoma.  Because the bladder is in contact with urine for extended periods, chemicals that become concentrated in the urine can cause [[bladder cancer]].  For example, [[cigarette smoking]] leads to the concentration of carcinogens in the urine and is a leading cause of bladder cancer. [[Aristolochic acid]], a compound found in plants of the family [[Aristolochiaceae]], also causes [[DNA]] mutations and is a cause of liver, urothelial and bladder cancers.<ref>{{cite journal|title=Mutation signatures implicate aristolochic acid in bladder cancer development|journal=Genome Medicine|volume=7|issue=1|pages=38|date=Dec 2015|doi=10.1186/s13073-015-0161-3|pmid=26015808|pmc=4443665|last1=Poon|first1=Song Ling|last2=Huang|first2=Mi Ni|last3=Choo|first3=Yang|last4=McPherson|first4=John R.|last5=Yu|first5=Willie|last6=Heng|first6=Hong Lee|last7=Gan|first7=Anna|last8=Myint|first8=Swe Swe|last9=Siew|first9=Ee Yan|last10=Ler|first10=Lian Dee|last11=Ng|first11=Lay Guat|last12=Weng|first12=Wen-Hui|last13=Chuang|first13=Cheng-Keng|last14=Yuen|first14=John SP|last15=Pang|first15=See-Tong|last16=Tan|first16=Patrick|last17=Teh|first17=Bin Tean|last18=Rozen|first18=Steven G. |doi-access=free }}</ref> Occupational exposure to certain chemicals is also a risk factor for bladder cancer. This can include [[aromatic amine]]s (aniline dye), [[polycyclic aromatic hydrocarbon]]s, and diesel engine exhaust.<ref>{{cite web|title=Bladder cancer risk factors|url=http://www.cancerresearchuk.org/cancer-info/cancerstats/types/bladder/riskfactors/bladder-cancer-risk-factors|website=Cancer Research UK|access-date=27 July 2014}}</ref>

===Carcinoma===
[[Carcinoma]] is a type of cancer that occurs in epithelial cells. [[Transitional cell carcinoma]] is the leading type of [[bladder cancer]], occurring in 9 out of 10 cases.<ref name="Bladder Cancer">American Cancer Society. (2014). Bladder cancer. Retrieved November 25, 2014, from http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-what-is-bladder-cancer {{Webarchive|url=https://web.archive.org/web/20161201201143/http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-what-is-bladder-cancer |date=2016-12-01 }}</ref> It is also the leading cause of cancer of the ureter, urethra, and [[urachus]], and the second leading cause of cancer of the kidney. Transitional cell carcinoma can develop in two different ways. Should the transitional cell carcinoma grow toward the inner surface of the bladder via finger-like projections, it is known as papillary carcinoma. Otherwise, it is known as flat carcinoma.<ref name="Bladder Cancer"/> Either form can transition from non-invasive to invasive by spreading into the muscle layers of the bladder. Transitional cell carcinoma is commonly multifocal, more than one tumor occurring at the time of diagnosis.

Transitional cell carcinoma can metastasize, or spread to other parts of the body via the surrounding tissues, the lymph system, and the bloodstream. It can spread to the tissues and fat surrounding the kidney, the fat surrounding the ureter, or, more progressively, lymph nodes and other organs, including bone. Common risk factors of transitional cell carcinoma include long-term misuse of pain medication, smoking, and exposure to chemicals used in the making of leather, plastic, textiles, and rubber.<ref name="Cleveland">Transitional Cell Cancer. (2012, April 13). Retrieved December 14, 2014, from https://my.clevelandclinic.org/health/diseases_conditions/hic_Transitional_Cell_Cancer_of_Renal_Pelvis_and_Ureter</ref>

Transitional cell carcinoma patients have a variety of treatment options. These include nephroureterectomy, or the removal of kidney, ureter, and bladder cuff, and segmental resection of the ureter. This is an option only when the cancer is superficial and infects only the bottom third of the ureter. The procedure entails removing the segment of cancerous ureter and reattaching the end.<ref name="Cleveland" /> Patients with advanced bladder cancer or disease, also often look to bladder reconstruction as a treatment. Current methods of bladder reconstruction include the use of gastrointestinal tissue. However, while this method is effective in improving the function of the bladder, it can actually increases the risk of cancer, and can cause other complications, such as infections, urinary stones, and electrolyte imbalance. Therefore, other methods loom in the future. For example, current research paves the way for use of pluripotent stem cells to derive urothelium, as they are highly and indefinitely proliferative in vitro (i.e. outside of the body).<ref name="Osborn" />

=== Interstitial cystitis ===
[[Interstitial cystitis]] (IC) a type of ''painful bladder syndrome'' is a chronic disease of the bladder that causes feelings of pressure and pain in the bladder among other symptoms which can range from mild to severe. Urinary frequency and urgency are the most common symptoms associated with the disease.<ref>{{Cite web|title=What is Interstitial Cystitis(IC)/Bladder Pain Syndrome? - Urology Care Foundation|url=https://www.urologyhealth.org/urology-a-z/i/interstitial-cystitis|access-date=2021-07-12|website=www.urologyhealth.org}}</ref> The exact causes of IC/BPS are unknown, but there is evidence of an association between increased permeability of the urothelium and IC.  Since the purpose of the urothelium is to act as a highly resistant barrier, the loss of this function has serious clinical implications.  Many patients with IC have exhibited a loss of [[Facet cell|umbrella cells]].<ref>{{Cite journal|last1=Hurst|first1=Robert E.|last2=Greenwood-Van Meerveld|first2=Beverley|last3=Wisniewski|first3=Amy B.|last4=VanGordon|first4=Samuel|last5=Lin|first5=HsuehKung|last6=Kropp|first6=Bradley P.|last7=Towner|first7=Rheal A.|date=October 2015|title=Increased bladder permeability in interstitial cystitis/painful bladder syndrome|journal=Translational Andrology and Urology|volume=4|issue=5|pages=563–571|doi=10.3978/j.issn.2223-4683.2015.10.03|issn=2223-4691|pmc=4706376|pmid=26751576}}</ref>

===Urothelial lesions===
*[[Papillary urothelial lesion]]s
** [[Papillary urothelial hyperplasia]]
** [[Urothelial papilloma]]
** [[Papillary urothelial neoplasm of low malignant potential]] ([[PUNLMP]])
** [[Low-grade papillary urothelial carcinoma]]
** [[High-grade papillary urothelial carcinoma]]
** [[Invasive urothelial carcinoma]]
* [[Flat urothelial lesion]]s
** [[Reactive urothelial atypia]]
** [[Urothelial inverted papilloma]]
** [[Urothelial atypia of unknown significance]]
** [[Urothelial dysplasia]]
** [[Urothelial carcinoma in situ]]
* Invasive [[urothelial carcinoma]]
** [[Invasive urothelial carcinoma]] ([[Not otherwise specified|NOS]])
** [[Urothelial carcinoma with inverted growth pattern]]
** [[Urothelial carcinoma with squamous differentiation]]
** [[Urothelial carcinoma with villoglandular differentiation]]
** [[Urothelial carcinoma, micropapillary variant]]
** [[Urothelial carcinoma, lymphoepithelioma-like variant]]
** [[Urothelial carcinoma, clear cell (glycogen-rich) variant]]
** [[Urothelial carcinoma, lipoid cell variant]]
** [[Urothelial carcinoma with syncitiotrophoblastic giant cells]]
** [[Urothelial carcinoma with rhabdoid differentiation]]
** [[Urothelial carcinoma similar to giant cell tumor of bone]]

==Gallery==
<gallery>
 File:Illu epithelium.jpg|Types of epithelium
 File:Illu_transitional_epithelium.svg|Schematic view of transitional epithelium
 File:Gray1141.png|Vertical section of bladder wall.
 File:Gray1134.png|Transverse section of ureter.
</gallery>

== See also ==
*[[List of distinct cell types in the adult human body]]
*[[List of human cell types derived from the germ layers]]

==References==
{{Reflist|2}}

===Bibliography===
* {{cite book|author=Andersson, Karl-Erik|title=Urinary Tract|publisher=Springer|year=2011|isbn=978-3-642-16498-9|url=https://books.google.com/books?id=jnfQ5VbxJ_AC}}

==External links==
* [https://web.archive.org/web/20061006141558/http://cellbio.utmb.edu/microanatomy/epithelia/transitional_epithelium.htm Histology at utmb.edu]
* {{OklahomaHistology|36_02}} - "ureter"
* {{OklahomaHistology|37_02}} - "urinary bladder"
* {{AnatomyAtlasesMicroscopic|02|24}} - "Transitional Epithelium", Ureter
* {{KansasHistology|urinary|renal16}} "ureter"
* [https://www.urothelium.com www.urothelium.com is an online resource for information about Human Urothelium and the "Biomimetic Urothelium"] {{Webarchive|url=https://web.archive.org/web/20110201125832/http://urothelium.com/ |date=2011-02-01 }}
* {{MeshName|Urothelium}}
* [https://courses.stu.qmul.ac.uk/smd/kb/microanatomy/humandev/answers/9a.htm Histology at qmul.ac.uk] {{Webarchive|url=https://web.archive.org/web/20110721232917/https://courses.stu.qmul.ac.uk/smd/kb/microanatomy/humandev/answers/9a.htm |date=2011-07-21 }}
* [http://www.med.umich.edu/urology/PatientInfo/Bladder/Staging.htm Diagram at umich.edu] {{Webarchive|url=https://web.archive.org/web/20060910182259/http://www.med.umich.edu/urology/PatientInfo/Bladder/Staging.htm |date=2006-09-10 }}
* [http://www.histology.wisc.edu/histo/res/desc/urinary/uriD25-26.htm Histology at wisc.edu] {{Webarchive|url=https://web.archive.org/web/20080610140953/http://www.histology.wisc.edu/histo/res/desc/urinary/uriD25-26.htm |date=2008-06-10 }}

{{Epithelial types}}
{{Authority control}}

[[Category:Epithelial cells]]