TRANSITIONAL EPITHELIUM: CHARACTERISTICS, FUNCTIONS AND PATHOLOGIES - ANATOMY AND PHYSIOLOGY - 2025

The transitional epithelium, known as the urothelium or uroepithelium, is the set of epithelial cells that cover the inner surface of the urinary ducts: from the renal calyces to the urethra. Previously, it was believed to be "transitional" because it allowed the gradual transition of the urinary tract lining from a stratified flat epithelium to a simple columnar epithelium.

However, advances in histology confirmed that it is a highly specialized and polymorphic type of epithelium, whose characteristics vary in the same individual depending on their location, state of the organ (empty or full) and function.

Location

The transitional epithelium is located inside the urinary tract, being the most superficial layer of the mucosa.

Anatomically it is located from the renal calyces (renal collecting system) to the urethra (excretory duct of urine), passing through the renal pelvis, ureters and bladder.

The thickness of the urothelium changes depending on the location, ranging from a couple of cell layers in the renal calyces to 6 or 8 layers in the urinary bladder.

characteristics

The microscopic characteristics of the epithelium may vary depending on the conditions of the duct they cover; that is, when the duct is full, the urothelium presents different characteristics than when it is empty.

Although all epithelia have a certain capacity to adapt to changes in volume, the transitional epithelium is the one that shows the greatest capacity for change, to the point that the most superficial cells can look completely flat (similar to that of the skin) when the Chute is very full, and then become cubic once it is empty.

Regardless of its location, the transitional epithelium has common characteristics in all areas where it is found, namely:

- It is a stratified epithelium.

- It is made up of three main cell layers (superficial, middle and basal).

Each layer of cells has specialized characteristics that allow it to carry out a specific function.

Superficial cells

They are polyhedral cells and, of all the layers of the urothelium, they are the ones that have the most capacity to modify their shape. At the microscopic level, they present specialized structures that allow them to fulfill two main functions: waterproofing and duct compliance.

These structures are a kind of plaque on the apical edge of the cell made up of a specialized protein called uroplakin. Said plates are joined together by a kind of hinge, these being the ones that allow it to change shape without breaking the joints.

In addition, surface cells possess very tight tight junctions (these are the junctions between the cell's side walls), a highly specialized surface glycan layer, and a special composition of the basement membrane. This layer can be made up of one to two layers of cells.

Middle cells

As their name indicates, they are located in the center of the thickness of the urothelium, grouped in 2 to 5 layers of cells (depending on the location) and with varied functions depending on the situation.

Under normal conditions, the middle cells contribute to the impermeability of the urinary ducts, because the cells are united by desmosomes, which are very dense and firm intercellular unions.

On the other hand, the cells of the middle layer of the transitional epithelium have the ability to differentiate and migrate towards the superficial layer, to replace those cells that have died and shed as part of the natural process of their life cycle.

This capacity is increased in the cases of trauma, irritating injuries and infections; therefore, the cells of the middle layer not only help with impermeability but also constitute a cellular reserve to replace cells of the more superficial layers when necessary.

Basal cells

It is the deepest group of cells and consists of a single layer of stem cells that differentiate and divide to give rise to cells in the upper layers.

Unlike the rest of the epithelia, there are no interdigitations between the underlying connective tissue and the basal cell layer, so the boundary between the basement membrane and the extracellular matrix is ​​flat.

Features

The transitional epithelium has two basic functions:

- Allow compliance of the urinary ducts.

- Waterproof the light (internal part) of said ducts.

If the transitional epithelium deteriorates or loses these capacities, it is impossible for the urinary tract to fully fulfill its functions.

Compliance

The apical plates of the urothelium are arranged with each other like tiles on a roof. However, unlike the latter, the urothelial plates are attached to each other by hinge-like structures that allow the plates to separate from each other without leaving gaps.

This characteristic is what allows the urinary ducts to dilate without disrupting the physical integrity of the mucosa; that is, pores are not opened where liquid could leak out of the duct.

Another characteristic that contributes not only to the urinary ducts being able to distend, but also to their tolerance of pressure very well is the type of intercellular junction.

Mid-cell desmosomes are a kind of "cement" that holds cells together despite duct distention. When this happens they change their arrangement (from several layers to fewer layers) and their morphology (from cubic or cylindrical to flat), but they do not separate from each other.

Impermeability

The combination of uroplakin plates, tight junctions, desmosomes, and layers of specialized glycans make leakage of urine from the urinary tract to the outside practically impossible.

On the other hand, the urothelium also functions as a barrier between the extracellular space, as well as in the capillary bed and in the lumen of the urinary ducts.

This is particularly important considering that the osmolarity of urine can be up to four times higher than that of plasma, so that without the presence of this barrier the water would pass from the extracellular space and the capillary bed to the bladder as a consequence. of osmosis.

This would not only alter the characteristics of the urine (diluting it) but would also produce an imbalance in the water balance.

Pathologies

The transitional epithelium, like any other epithelium, is exposed to two main types of pathology: infections and the development of neoplasms (cancer).

When the transitional epithelium is colonized by bacteria, it is called a urinary infection, the most frequent cause being E. coli, although infections by other gram negative germs as well as fungi can occur.

With regard to neoproliferative diseases, cancer that begins in the urothelium (mainly bladder cancer) is usually of the carcinoma type, characterized by being very aggressive.

Finally, there is a condition that exclusively affects the urothelium, which is known as interstitial cystitis. Clinically the symptoms are identical to those of a lower urinary tract infection, although urine cultures are negative.

The cause of this condition is not yet known although it is believed that it may be due to certain unidentified molecular alterations in the urothelium.

References

1. Mostofi, FK (1954). Potentialities of bladder epithelium. The Journal of urology, 71 (6), 705-714.
2. Hicks, RM (1966). The permeability of rat transitional epithelium: keratinization and the barrier to water. The Journal of cell biology, 28 (1), 21-31.
3. Hicks, RM (1965). The fine structure of the transitional epithelium of rat ureter. The Journal of cell biology, 26 (1), 25-48.
4. Mysorekar, IU, Mulvey, MA, Hultgren, SJ, & Gordon, JI (2002). Molecular regulation of urothelial renewal and host defenses during infection with uropathogenic Escherichia coli. Journal of Biological Chemistry, 277 (9), 7412-7419.
5. Wein, AJ, Hanno, PM, & Gillenwater, JY (1990). Interstitial cystitis: an introduction to the problem. In Interstitial cystitis (pp. 3-15). Springer, London.
6. Sant, GR, & Theoharides, TC (1994). The role of the mast cell in interstitial cystitis. The Urologic clinics of North America, 21 (1), 41-53.
7. Wai, CY, & Miller, DS (2002). Urinary bladder cancer. Clinical obstetrics and gynecology, 45 (3), 844-854.
8. Amin, MB (2009). Histological variants of urothelial carcinoma: diagnostic, therapeutic and prognostic implications. Modern Pathology, 22 (S2), S96.