Biologia 67/5: 1018—1025, 2012
Section Zoology
DOI: 10.2478/s11756-012-0090-1
Options for histological study of the structure and ultrastructure
of human urinary bladder epithelium
Štefan Polák1, Stanislav Žiaran2, Jana Mištinová3, Katarína Bevízová4,
Ľuboš Danišovič5 & Ivan Varga1
1
Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, Slovakia; e-mail:
[email protected]
2
Department of Urology, Faculty of Medicine and University Hospital, Comenius University in Bratislava, Slovakia
3 st
1 Department of Radiology, Faculty of Medicine and University Hospital, Comenius University in Bratislava, Slovakia
4
Institute of Anatomy, Faculty of Medicine, Comenius University in Bratislava, Slovakia
5
Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava,
Slovakia
Abstract: The urothelium lines all urinary passages, with exception of the distal portions of the urethra. For the first time
the structure of the human bladder was described by Leonardo Da Vinci in 15th century, however, the exact ultrastructure
and function of the bladder’s epithelium have not been fully understood. The aim of our study was to investigate the structure
of normal human urinary bladder epithelium with methods of classical histology, transmission electron microscopy (TEM)
and scanning electron microscopy (SEM). We obtained biopsies from non-tumor areas from the human urinary bladder
of tumor-bearing patients during transurethral resections of these tumours in general or spinal anaesthesia. Totally we
investigated biopsies from 20 patients, 16 males and 4 females. The mean age of this group of patients was averaged 66.5
years. The urothelium is comprised of three cell types including polyhedral basal cells, piriform intermediate cells, and
superficial umbrella cells. In human urinary bladder epithelium we found a direct connection between intermediate cells and
the basement membrane. These thin cytoplasmic projections are detectable not only on slides for light microscopy (semithin sections), but also in transmission electron-micrographs. In semi-thin sections we found also direct connections between
superficial umbrella cells and basement membrane. These connections we were not able to verify via transmission electronmicroscopy. Nevertheless our results show that the human urinary bladder urothelium is a special type of pseudostratified
epithelium and each cell has a thin cytoplasmic projection with a direct contact with basement membrane.
Key words: human urinary bladder; transitional epithelium; light microscopy, transmission and scanning electron microscopy, ultrastructure
Introduction
The urinary bladder epithelium (urothelium or transitional epithelium, lat. epithelium transitionale) is located at the interface between the urine and the underlying loose connective tissue, where it forms a highresistance barrier to ions, solutes, and water, as well
as pathogens. Historically, the urothelium had been
viewed as a passive barrier. However, recent evidence
has demonstrated that it can modulate the composition of the urine, and it functions as an integral part of
a sensory web in which it receives, amplifies, and transmits information about its external milieu to the underlying nervous and muscular systems (Birder 2004;
Lazzeri 2006; Khandelwal et al. 2009). The urothelium
possesses four properties to perform these functions.
First, it offers a minimum epithelial surface area-tourine volume; this reduces the surface area for passive
movement of substances between lumen and blood. Secc 2012 Institute of Zoology, Slovak Academy of Sciences
ond, the passive permeability of the apical membrane
and tight junctions is very low to electrolytes and nonelectrolytes. Third, the urothelium has a hormonally
regulated sodium absorptive system; thus passive movement of sodium from blood to urine is countered by active sodium re-absorption. Last, the permeability properties of the apical membrane and tight junctions of the
urothelium are not altered by most substances found in
the urine or blood (Lewis 2000).
The urothelium lines all urinary passages, with
exception of the distal termination of the urethra in
males and mid and distal portion of the urethra in
females. Urothelium is composed of a basal layer
(stratum basale), followed by an intermediated layer
(stratum intermedium) and superficial layer (stratum superficiale), which consist of often binucleate umbrella cells (urotheliocytus superficialis, umbellocytus). The umbrella cells are interconnected by tight
junctions (which are composed of multiple proteins such
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The structure of human bladder epithelium
as the claudins) and are covered on their apical surface by crystalline proteins called uroplakins (granulum uroplakini) that assemble into hexagonal urothelial plaques (crusta urothelialis) (Birder 2011). In some
species, such as rat and guinea pig, the umbrella cells
and also the intermediate cells have projections to the
basement membrane (Apodaca 2004). But controversy,
concerning the classification of this epithelium in human in different textbooks, is remarkable. According to
some authors (e.g., Krstić 1979, 1988, 1994; Kierszenbaum 2007), it is a pseudostratified epithelium; since
fine processes of superficial umbrella cells also contact
the basal lamina. Others (e.g., De Groat 2004; Ross &
Pawlina 2006; Young et al. 2006; Gartner & Hiatt 2007;
Eroschenko 2008; Ovalle & Nahirney 2008; Cui et al.
2011; Gartner et al. 2011) regard the human bladder
epithelium as a stratified epithelium with more than
one layer of epithelial cells.
The aim of our study was to investigate the structure of normal human urinary bladder epithelium with
methods of classical histology, transmission electron
microscopy (TEM) and scanning electron microscopy
(SEM). We searched for the answer to long-term unclear question: is the human urinary bladder mucosa
covered by stratified or pseudostratified type of epithelium?
Patients and methods
We obtained biopsies from non-tumor areas from the human urinary bladder of tumor-bearing patients during
transurethral resections of these tumours in general or spinal
anaesthesia. Totally we investigated biopsies from 20 patients, 16 males and 4 females. The mean age of this group
of patients was averaged 66.5 years, ranging from 46 to 84
years. The most frequent diagnosis was urothelial (transitional) carcinoma, which is the most common urinary bladder malignancy.
For ordinary light microscopy (LM), we fixed the samples for 24 h in 4% formaldehyde, for transmission (TEM)
and scanning electron microscopy (SEM) for 3 h in 3% glutaraldehyde. For LM we embedded samples into paraffin. We
stained the 5 µm thin sections by hematoxyline and eosin
(HE), Masson’s trichrome-method, Periodic Acid Schiff reaction (PAS) for demonstrating of polysaccharides and the
Gömöris’ impregnation method for visualisation of reticular fibres (Lillie 1965). For TEM we post-fixed the tissue
with 1% OsO4 in phosphate buffering solution and embedded into Durcupan ACM. The 1µm semithin sections were
stained with toluidine blue. The ultrathin sections were contrasted with uranyl acetate and lead citrate. For SEM we
identically postfixed the tissue, after dehydration we dried
it at the critical point of CO2 (CPD 020 Balzers Union) and
galvanized it with gold for 2.5 min at the pressure of 2500 Pa
and the current of 50 mA in the apparatus SCD 030 Balzers Union, the anode-cathode distance being 55 mm (Polák
et al. 2009; Gálfiová et al. 2009).
Light microscopic examination was performed by
Nikon Eclipse 80i microscope and images were captured
with Nikon DS-Fi1 digital camera. For TEM we used microscope MORGAGNI 268D and for SEM analysis we used
microscope VEGA TS 5136 XM.
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Results
Light microscopy
In basic histological staining (HE and Masson’s trichrome method) the urothelium consisted of 4–6 cell
layers; the layer of polyhedral basal cells, one or more
layers of piriform intermediate cells and the superficial
layer of large umbrella cells (Figs 1–3). Umbrella cells
were often binucleated (Fig. 3) and their nuclei contained more than one nucleoli. The smallest, polyhedral
urothelial cells were observed in the basal layer (around
10 µm in diameter), the largest cells in the surface layer
(more than 100 µm in diameter). The apparent number of cell layers was in part related to the plane of section through the urothelium (compare Figs 2 and 3). In
case of careful dehydratation, embedding and sectioning, there were no artificial spaces between urothelial
cells (Figs 1, 2). But the urothelium was very sensitive
to histological processing and the shrinkage of cells often formed artificial intercellular spaces and ruptures
(Fig. 3). The loose connective tissue of lamina propria
lied under urothelium in which numerous blood capillaries (Fig. 1), free lymphocytes and lymphoid follicles
were observed. The basal membrane between urothelium and lamina propria is well visualized after silver
impregnation; we observed numerous reticular fibers in
the lamina reticularis (Fig. 4). The basal membrane
and the apical surface of superficial umbrella cells were
PAS positive; the PAS reaction was stronger in the apical surface of urothelium (Fig. 5).
The fine structure of urothelium was better observed in semi-thin sections after staining with toluidine blue (Figs 6–8). The connections between intermediate cells and basal membrane were evident, but we often found direct connections via long processes between
superficial cells and basal membrane, too. It shows that
urothelium consists only from one layer of morphologically different cells and each epithelial cell reaches the
basal membrane (a special type of pseudostratified epithelium). The superficial umbrella cells were lighter,
but near the apical surface contained small darker granules or vesicles (Fig. 7).
Scanning electron microscopy
In scanning electron microscopy the normal urinary
bladder epithelium consists of large, flat polygonal cells
(Fig. 9). The surface of the umbrella cells appears
pleated and each cell is surrounded by tight junctions.
The plasma membrane of umbrella cells looks scalloped.
Higher magnification views show that the surface is covered by raised ridges, also called hinges (microplicae),
and intervening areas called plaques.
Transmission electron microscopy
The basal cells create a single layer of polyhedral cells
(10–20 µm in diameter) with round and pale nucleus
(Fig. 10). In cytoplasm clusters of mitochondria are visible. The number of intermediate cell layers is variable
and varies from one to four. They are piriform in shape
and have thin cytoplasmic processes (often more than
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Š. Polák et al.
Figs 1–8. 1: The urinary bladder’s mucosa of 70–year-old man. The mucosa is composed of transitional epithelium with morphologically
different type of cells and loose connective tissue of lamina propria with many blood vessels. UC – umbrella cells, IC – intermediate
cells, BC – basal cells, BM – basal membrane, LP – lamina propria, BV – blood vessel (hematoxylin & eosin, magn. ×400). 2: The
urinary bladder’s mucosa of 61-year-old man. The umbrella cells (UC) of transitional epithelium have typical dome shape. Lamina
propria (LP) contains thin collagen fibers (green) and many fixed and wandering cells (their nuclei are black). (Masson’s trichrome,
magn. ×400). 3: Oblique section of transitional epithelium of the same patient as in Fig. 2. (the number of cell layers is higher).
Umbrella cells (UC) often contain two nuclei (arrows). The urothelium is very sensitive to histological processing and the shrinkage of
cells often forms artificial intercellular spaces and ruptures. LP – lamina propria (Masson’s trichrome, magn. ×400). 4: The urinary
bladder’s mucosa of 62–year-old man after silver impregnation. The basal membrane contains numerous thin and branched reticular
fibers (RF). TE – transitional epithelium, AS – apical surface (Gömöris’ impregnation method, magn. ×400). 5: The urinary bladder’s
mucosa of 62-year-old man after visualization of polysaccharides. The basal membrane (BM) and the apical surface (AS) of umbrella
cells are PAS positive (PAS-reaction, magn. ×400). 6: Semithin (1 µm thick) section throughout the mucosa of urinary bladder of 61year-old man. The arrows point to the complete cytoplasmatic processes by which superficial cells reach the basal membrane. BV –
blood vessels (toluidine blue, magn. ×400). 7: Semithin (1 µm thick) section throughout the mucosa of urinary bladder of 61-year-old
man. The arrows point to the complete cytoplasmatic process by which intermediate cells reach the basal membrane. The umbrella
cells (UC) are lighter, but they contain numerous basophilic granules (toluidine blue, magn. ×400). 8: Tangential semithin (1 µm
thick) section throughout the mucosa fold of urinary bladder of 88–year-old man. The arrows point to the complete cytoplasmatic
processes by which intermediate cells reach the basal membrane. BV – blood vessel (toluidine blue, magn. ×400).
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The structure of human bladder epithelium
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Figs 9–12. 9: The surface of flat polygonal umbrella cells is covered by raised ridges, also called hinges (microplicae), and intervening
areas called urothelial plaques. Each cell is surrounded by tight junctions (arrows). (SEM, magn. ×5,000). 10: Small, polyhedral basal
cells form a deep single layer of urothelium. Under urothelium is loose connective tissue of lamina propria with collagen fibers. BC
– basal cells, BL – basal lamina (TEM, line in Fig. = 2 µm, magn. ×5,600). 11: Piriform intermediated cells of urothelium with
long, thin cytoplasmic processes that connect them to the basal membrane. Each nucleus has a deep invagination. In the basal part
cytoplasm contains abundant mitochondria. N – nucleus, M – mitochondria, En – endothelium of capillary, Er – erythrocyte (TEM,
magn. ×3,500). 12: Detail on the basal part of cytoplasmic processes (arrows) of an intermediate cell with numerous mitochondria. M
– mitochondria, LB – lamina basalis, N – nucleus of basal cell (TEM, magn. ×7,100).
30 µm long) that connect them directly to the basement membrane (Fig. 11). Their nuclei have deep invaginations and prominent nucleoli. The basal parts of
cytoplasmic processes contain abundant mitochondria
(Fig. 12), which may reflex their ion-transport function.
The superficial layer of urothelium is composed of
large flat, polygonal umbrella cells with well-developed
leafy microridges covering the surface of the cells. These
cells are often binucleated and have long cytoplasmic
projections between intermediate cells (Fig. 13). But
we did not observe direct connections of these projections with basal lamina by this method. In the future
we will use much more serial sections for detection of
direct connection between superficial layer and basal
lamina. Transmission electron-micrograph of cross sectioned umbrella cell apical membrane demonstrates
hinges and urothelial plaques (Fig. 14). The epithelium possessed an asymmetric unit membrane at the
apical cell surface and many discoid (fusiform) vesicles
(vesiculae adluminaless urotheliales), which are formed
from the surface membrane when the bladder is in relaxed state. We found numerous tight junctions, strong
desmosomal contact (Fig. 15), and lateral cell membrane reserve in the form of extensive interdigitations
which probably plays an important role during bladder distension. Desmosomes indicate that these cells
are strongly attached to each other, precluding any sliding movement between cells. The cytoplasm of umbrella
cells is pale, and contains numerous lipid droplets, mitochondria (mostly in the apical part), Golgi apparatus and rough endoplasmic reticulum (Fig. 16). We
found also numerous lamellar or multivesicular bodies in the cytoplasm of umbrella cells (Figs 16–18).
They are probably tertiary lysosome, contain also lipid
droplets and are involved in uroplakin degradation process.
Urothelium: stratified or pseudostratified epithelium
In human urinary bladder epithelium we found a direct
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Š. Polák et al.
Figs 13–18. 13: Superficial binucleated umbrella cell with thin long cytoplasmic process (arrows) that connects it probably to the basal
lamina. A – apical surface, N – nucleus, L – lipid droplet (TEM, magn. ×4,400). 14: Apical surface of umbrella cell. In cytoplasm
there are many discoid vesicles (vesicula adluminalis urothelialis), which are formed from the surface membrane when the bladder is in
relaxed state. AUM – asymmetrical unit membrane (TEM, magn. ×22,000). 15: Junctional complex between two neighboring umbrella
cells, desmosome (D) and tight junction (TJ). G – glycogen granules, N – nucleus (TEM, line in Fig. = 0.2 µm, magn. ×71,000). 16:
Cytoplasm of umbrella cells with well-developed rough endoplasmic reticulum and numerous mitochondria. M – mitochondria, rER –
rough endoplasmic reticulum, LB – lamellar body, N – nucleus (TEM, magn. ×22,000). 17: Lamellar body with numerous lipid droplets
from cytoplasm of an umbrella cell. M – mitochondria, N – nucleus, L – lipid droplet (TEM, magn. ×14,000). 18: Extremely large
lamellar body from cytoplasm of an umbrella cell. AUM – apical surface covered by asymmetrical unit membrane, M – mitochondria,
L – lipid droplets, R – ribosomes (TEM, magn. ×14,000).
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The structure of human bladder epithelium
ment membrane. These thin cytoplasmic projections
are detectable not only on slides for light microscopy
(semi-thin sections), but also in transmission electronmicrographs. In semi-thin sections we found also direct
connections between superficial umbrella cells and basement membrane. These connections we were not able to
verify via transmission electron-microscopy. Nevertheless our results show that the human urinary bladder
urothelium is a special type of pseudostratified epithelium and each cell has a thin cytoplasmic projection
with a direct contact with basement membrane.
Discussion
The urothelium separates the urinary tract lumen from
underlying tissues of the urinary tract wall. Previously
considered as a merely effective barrier between these
two compartments it is now recognized as more active
tissue that senses and transduces information about
physical and chemical conditions within the urinary
tract, such as luminal pressure and urine composition
(Border et al. 2010). Blood-urine barrier is the tightest and most impermeable barrier in the body. In the
urinary bladder, the barrier must accommodate large
changes in the surface area during distensions and contractions of the organ (Kreft et al. 2010a).
The morphology of mammalian bladder epithelium
has been documented in several classical histological
studies, but most of them are from 60‘ and 70‘ of the
last century. Classical methods of light microscopy were
used in studies by Leeson (1962) and Ersoy et al. (2006)
in rats and Jost et al. (1989) in humans. The methods of electron microscopy were used by Walker (1960)
in mice, Burke (1976) and Verlander (1998) in rats,
Richter & Moize (1963) in different mammalians, Monis
& Zambrano (1968) in humans and Hoyes et al. (1972)
in human fetuses. In our work we described some histological methods (light microscopy, transmission and
scanning electron microscopy) used for investigation of
ultrastructure of human’s urinary epithelium. Our observations are in agreement with the schematic drawings of ultrasctucture of human urothelium published
by Krstić (1979, 1988, 1994).
A fundamental limitation in the use of human
tissue in medical research is the artifact induced by
rapid post mortem autolysis (Jost et al. 1989). This applies particularly to the bladder epithelium and may be
the underlying case for several disproportionate morphological description of “normal” urothelium. Urothelium is exposed to the permanent effect of acidic
urine; therefore the bladder epithelium undergoes rapid
post mortem degradation. In animal models, autolytic
changes are morphologically detectable by scanning
electron microscopy within 60 seconds after euthanasia of the animals (Cohen et al. 2007). In our study, the
bladder epithelium was extracted peroperatively and
immediately fixed within less than ten seconds.
The uroepithelium is comprised of three cell types
including basal cells, intermediate cells, and umbrella
cells. Basal cells are small, form a single layer that
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contacts the underlying connective tissue and capillary bed, and serve as precursors for the other cell layers. Basal cells normally exhibit a low (3–6 months)
turnover rate, in fact the slowest turnover of any mammalian epithelial cells (Martin 1972; Hicks 1975). Jost
et al. (1989) found no mitoses despite a careful search
covering about 50,000 urothelial cells. Intermediate
cells are piriform in shape, sit on top of the underlying basal cells, and form a layer that appears in crosssection anywhere from one to several cell layers thick.
The outermost umbrella cell layer is comprised of very
large polyhedral cells. Although umbrella cells are long
living, they are rapidly regenerated when the urothelium is damaged. This regeneration can result from cell
division within any of the three cell layers, and generation of the multinucleate umbrella cells is likely the
result of intermediate cell-cell fusion (Apodaca 2004).
The superficial umbrella cells are interesting from
several points of view. These cells are greatly flattened and expanded, with a diameter reaching over
100 µm (Veranic et al. 2004). Well developed tight
junctions and desmosomes are found between umbrella
cells and are visible also in our scanning and transmission electron-micrographs. These junctions are a basis
for the paracellular permeability barrier of the bladder against diffusion of urinary solutes (Rickard et al.
2008). The umbrella cells have a characteristic fatty
acid metabolism. The fatty acid composition of microsomal, mitochondrial, cytosolic, and plasma membrane
subcellular fractions showed a distinctive lipid composition compared to the general profile of plasma membrane from other tissues (Calderon et al. 1998). Using transmission electron microscopy we found numerous lipid droplets in the cytoplasm of umbrella cells,
nearby the apical surface, which may reflect the unique
morphology of these cells, consisting of plaques with an
asymmetrical membrane unit.
The apical surface of mammalian urothelium is
highly specialized, featuring two-dimensional crystals
(asymmetrical membrane units, urothelial plaques)
containing four major uroplakin-particles (Oostergetel
et al. 2001; Min et al. 2003; Kong et al. 2004). The differentiation of urothelial cells starts with the synthesis
of differentiation-related proteins, i.e., cytokeratins and
uroplakins, and later with their specific organization.
Veranic et al. (2004) consider that the umbrella cell has
reached its final stage of differentiation when uroplakins
form plaques of asymmetric unit membrane that are inserted into the apical plasma membrane. From cytological point of view, the Golgi apparatus has an essential
role in membrane trafficking, determining the assembly
and delivery of uroplakins to the apical plasma membrane) of superficial urothelial cells of urinary bladder
(Kreft et al. 2010b). Although urothelial plaques and
attendant asymmetrical unit membranes particles have
been known for decades, the role of these structures
is not well understood. A function of plaques is that
they may help maintain the permeability barrier associated with the apical membrane of umbrella cells.
Recent biophysical analyses demonstrate that bladders
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1024
from knockout animals have a significant increase in
water and urea permeability across the umbrella cell
layer; however, junctional permeability appeared to be
unchanged (Hu et al. 2002). Another function described
more than 50 years ago to plaques is that they may
modulate the apical surface area of the umbrella cell by
regulating insertion (during filling) and recovery (during voiding) of plaque membrane (Porter et al. 1967).
Several specific agents have been identified as urinary bladder carcinogens in humans. Classes of chemical agents that are associated with bladder cancer
include aromatic amines and amides, phosphoramide
mustards, nitrosamines, arsenicals, and various alkylating and cancer chemotherapeutic agents. In addition,
chronic bacterial cystitis and schistosomiasis have been
associated with an increased risk of bladder cancer, and
there is some evidence that long-standing lower urinary
tract calculi can lead to an increased risk of bladder
cancer (Cohen 1998; Cohen et al. 2007).
Our work described the normal structure of human urinary bladder epithelium and can be useful also
for other experimental works focused on morphological
changes of urothelium under various conditions. The
first signs of epithelial cells malignant abnormalities are
detectable in the basal layer. These cells have nuclear
abnormalities such as increased nucleus/cytoplasm ratio, eccentric nucleus, hyperchromatism and/or irregular shape. Their occurrence in small number does not
allow their categorization as malignant and they are
termed as atypical urothelial cells (Piaton et al. 2011).
The occurrence of atypical urothelial cells has a diagnostic and prognostic value. The information about
normal structure of the wall of urinary bladder is also
important for regenerative medicine, during testing of
artificial scaffolds used in surgical bladder reconstitution (De Angeli et al. 2004).
Conclusion
In our work we described the fine structure of normal human urinary bladder epithelium with methods
of classical histology, transmission electron microscopy
and scanning electron microscopy. In human urinary
bladder epithelium we found (light and electron microscopically) a direct connection between intermediate
cells and the basement membrane. In semi-thin sections
we found also direct connections between the superficial umbrella cells and basement membrane. Our results
show that the human urinary bladder urothelium is a
special type of pseudostratified epithelium and each cell
has a thin cytoplasmic projection with a direct contact
with basement membrane.
References
Apodaca G. 2004. The uroepithelium: Not just a passive barrier.
Traffic 5 (3): 117–128. DOI: 10.1046/j.1600-0854.2003.00156.
x
Birder L. 2004. Role of the urothelium in bladder function. Scand.
J. Urol. Nephrol. 38: 48–53. DOI: 10.1080/03008880410015
165
Š. Polák et al.
Birder L.A. 2011. Urothelial signaling, pp. 207–231. In: Andersson K.-E. & Michel M.C. (eds), Urinary Tract. Handbook
of Experimental Pharmacology 202, Springer, Heidelberg –
New York. ISBN: 978-3-642-16498-9, DOI: 10.1007/978-3642-16499-6 10
Birder L.A., Kanai A.J., Cruz F., Moore K. & Fry C.H. 2010. Is
the urothelium intelligent? Neurourol. Urodyn. 29 (4): 598–
602. DOI: 10.1002/nau.20914
Burke J.A. 1976. Scanning electron microscopy of the urinary
tract. Clin. Nephrol. 6 (2): 329–334.
Calderon R.O., Glocker M. & Eynard A.R. 1998. Lipid and
fatty acid composition of different fractions from rat urinary
transitional epithelium. Lipids 33 (10): 1017–1022. DOI:
10.1007/s11745-998-0300-0
Cohen S.M. 1998. Urinary bladder carcinogenesis. Toxicol.
Pathol. 26 (1): 121–127. DOI: 10.1177/019262339802600114
Cohen S.M., Ohnishi T., Clark N.M., He J. & Arnold L.L. 2007.
Investigations of rodent urinary bladder carcinogens: collection, processing, and evaluation of urine and bladders. Toxicol. Pathol. 35 (3): 337–347. DOI: 10.1080/01926230701197
115
Cui D., Naftel J.P., Lynch J.C., Yang G., Daley W.P., Haines
D.E. & Fratkin J.D. 2011. Atlas of Histology with Functional
and Clinical Correlations, First Edition. Lippincott Williams
& Wilkins, Baltimore, 439 pp. ISBN: 0-7817-9759-4, 978-0781-797597
De Angeli S., Del Pup L., Fandella A., Di Liddo R., Anselmo G.,
Macchi C., Conconi M.T., Parnigotto P.P. & Nussdorfer G.G.
2004. New experimental models for the in vitro reconstitution
of human bladder mucosa. Int. J. Mol. Med. 14 (3): 367–372.
De Groat W.C. 2004. The urothelium in overactive bladder: passive bystander or active participant? Urology 64 (Suppl.
6A): 7–11. DOI: 10.1016/j.urology.2004.08.063
Eroschenko V.P. 2008. diFiore’s Atlas of Histology with Functional Correlations. 11th Edition. Lippincott Williams &
Wilkins, Baltimore, 532 pp. ISBN: 0781770572, 978-0781770
576
Ersoy Y., Ercan F. & Cetinel S. 2006. A comparative ontogenic
study of urinary bladder: impact of the epithelial differentiation in embryonic and newborn rats. Anat. Histol. Embryol.
35 (6): 365–374. DOI: 10.1111/j.1439-0264.2006.00699.x
Gálfiová P., Varga I., Kopáni M., Michalka P., Michalková J.,
Jakubovský J. & Polák Š. 2009. Some possibilities of representing microcirculation in human spleen. Biologia 64 (6):
1242–1246. DOI: 10.2478/s11756-009-0193-5
Gartner L.P. & Hiatt J.L. 2007. Color Textbook of Histology. Third Edition. Saunders Elsevier, Philadelphia, 573 pp.
ISBN: 9781416029458
Gartner L.P., Hiatt J.L. & Strum J.M. 2011. Cell Biology and
Histology. Sixth Edition. Lippincott Williams & Wilkins, Baltimore, 374 pp. ISBN: 1608313212, 978-1608313211
Hicks M. 1975. The mammalian urinary bladder: an accomodating organ. Biol. Rev. 50 (2): 215–246. DOI: 10.1111/j.1469185X.1975.tb01057.x
Hoyes A.D., Ramus N.I. & Martin B.G.H. 1972. Fine structure
of the epithelium of the human fetal bladder. J. Anat. 111
(3): 415–425. PMID: 1271131
Hu P., Meyers S., Liang F.X., Deng F.M., Kachar B., Zeidel
M. & Sun T.T. 2002. Role of membrane proteins in permeability barrier function: uroplakin ablation elevates urothelial permeability. Am. J. Physiol. 283: F1200-F1207. DOI:
10.1152/ajprenal.00043.2002.
Jost S.P., Gosling J.A. & Dixon J.S. 1989. The morphology of
normal human bladder urothelium. J. Anat. 167: 103–115.
PMID: 1256824
Khandelwal P., Abraham S.N. & Apodaca G. 2009. Cell biology and physiology of the uroepithelium. Am. J. Physiol. Renal. Physiol. 297: F1477–F1501. DOI: 10.1152/ajprenal.00327.2009
Kierszenbaum A.L. 2007. Histology and Cell Biology. An Introduction to Pathology. Second Edition. Mosby Elsevier,
Philadelphia, 671 pp. ISBN: 9780323045278
Kong X.T., Deng F.M., Hu P., Liang F.X., Zhou G., Auerbach A.B., Genieser N., Nelson P.K., Robbins E.S., Shapiro
E., Kachar B. & Sun T.T. 2004. Roles of uroplakins in
Unauthenticated
Download Date | 6/15/17 5:30 PM
The structure of human bladder epithelium
plaque formation, umbrella cell enlargement, and urinary
tract diseases. J. Cell Biol. 167 (6): 1195–1204. DOI:
10.1083/jcb.200406025
Kreft M.E., Hudoklin S., Jezernik K. & Romih R. 2010a. Formation and maintenance of blood-urine barrier in urothelium. Protoplasma. 246 (1–4): 3–14. DOI: 10.1007/s00709010-0112-1
Kreft M.E., Di Giandomenico D., Beznoussenko G.V., Resnik N.,
Mironov A.A. & Jezernik K. 2010b. Golgi apparatus fragmentation as a mechanism responsible for uniform delivery of uroplakins to the apical plasma membrane of uroepithelial cells.
Biol. Cell. 102 (11): 593–607. DOI: 10.1042/BC20100024
Krstić R.V. 1979. Ultrastructure of the Mammalian Cell. An Atlas. Springer-Verlag, Berlin, 376 pp. ISBN: 3540095837, 9783540095835
Krstić R.V. 1988. Die Gewebe des Menschen und der Säugetiere.
Ein Atlas zum Studium für Mediziner und Biologen. SpringerVerlag, Berlin, 399 pp. ISBN-10: 3540190074
Krstić R.V. 1994. Human Microscopic Anatomy. An Atlas for
Students of Medicine and Biology. Springer-Verlag, Berlin,
615 pp. ISBN-10: 0387536663
Lazzeri M. 2006. The physiological function of the urothelium –
more than a simple barrier. Urol. Int. 76 (4): 289–295. DOI:
10.1159/000092049
Leeson C.R. 1962. Histology, histochemistry and electron microscopy of the transitional epithelium of the rat urinary bladder in response to induced physiological changes. Acta Anat.
48: 297–315. PMID: 13929206
Lewis S.A. 2000. Everything you wanted to know about the bladder epithelium but were afraid to ask. Am. J. Physiol. Renal.
Physiol. 278 (6): F867–F874. PMID: 10836974
Lillie R.D. 1965. Histopathologic Technic and Practical Histochemistry. 3rd Edition. McGraw-Hill book company, New
York, 715 pp. ISBN: 0070378614
Martin B.F. 1972. Cell replacement and differentiation in transitional epithelium: a histological and autographical study of
the guinea-pig bladder and ureter. J. Anat. 112 (3): 433–
455. PMID: 1271184
Min G., Zhou G., Schapira M., Sun T.T. & Kong X.P. 2003.
Structural basis of urothelial permeability barrier function as
revealed by Cryo-EM studies of the 16 nm uroplakin particle.
J. Cell. Sci. 116 (20): 4087–4094. DOI: 10.1242/jcs.00811
Monis B. & Zambrano D. 1968. Ultrastructure of the transitional
epithelium of man. Zeitsch. Zellforsch. 87 (1): 101–117. DOI:
10.1007/BF00326563
1025
Oostergetel G.T., Keegstra W. & Brisson A. 2001. Structure of
the major membrane protein complex from urinary bladder
epithelial cells by cryo-electron crystallography. J. Mol. Biol.
314 (2): 245–252. DOI: 10.1006/jmbi.2001.5128
Ovalle W.K. & Nahirney P.C. 2008. Netter’s Essential Histology.
Saunders Elsevier, Philadelphia, 493 pp. ISBN: 1929007868,
9781929007868
Piaton E., Advenier A.S., Benaďm G., Petrucci M.D., Lechevallier F.M. & Ruffion A. 2011. Atypical urothelial cells
(AUC): A Bethesda-derived wording applicable to urinary cytopathology. Ann. Pathol. 31 (1): 11–17. DOI:
10.1016/j.annpat.2010.09.010
Polák Š., Gálfiová P. & Varga I. 2009. Ultrastructure of human
spleen in transmission and scanning electron microscope. Biologia. 64 (2): 402–408. DOI: 10.2478/s11756-009-0046-2
Porter K., Kenyon K. & Badenhausen S. 1967. Specializations of
the unit membrane. Protoplasma. 63 (1–3): 262–274. DOI:
10.1007/BF01248042
Richter W.R. & Moize S.M. 1963. Electron microscopic observations on the collapsed and distended mammalian urinary
bladder (transitional epithelium). J. Ultrastruct. Res. 9 (1–
2): 1–9. DOI: 10.1016/S0022-5320(63)80032-5
Rickard A., Dorokhov N., Ryerse J., Klumpp D.J. & McHowat J.
2008. Characterization of tight junction proteins in cultured
human urothelial cells. In Vitro Cell. Dev. Biol. Animal. 44
(7): 261–267. DOI: 10.1007/s11626-008-9116-y
Ross M.H. & Pawlina W. 2006. Histology. A Text and Atlas.
With correlated cell and molecular biology. Fifth Edition.
Lippincott Williams & Wilkins, Baltimore, 906 pp. ISBN:
0781772214, 978-0781772211
Veranic P., Romih R. & Jezernik K. 2004. What determines differentiation of urothelial umbrella cells? Eur. J. Cell Biol. 83
(1): 27–34. DOI: 10.1078/0171-9335-00351
Verlander J.W. 1998. Normal ultrastructure of the kidney and
urinary tract. Toxicol. Pathol. 26 (1): 1–17. PMID: 9502381
Walker B.E. 1960. Electron microscopic observations of transitional epithelium of the mouse urinary bladder. J. Ultrastruct. Res. 3 (4): 345–361. DOI: 10.1016/S0022-5320(60)
90014-9
Young B., Lowe J.S., Stevens A. & Heath J.W. 2006. Wheater’s
Functional Histology: A Text and Colour Atlas. Fifth Edition. Churchill Livingstone, Philadelphia, 448 pp. ISBN:
044306850X, 978-0443068508
Received January 12, 2012
Accepted March 21, 2012
Unauthenticated
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