The urinary bladder( fig 1) is a musculomembranous sac situated retroperitoneally
in the pelvic cavity posterior to the symphysis pubis. In females, the bladder is
positioned anterior to the uterus and vagina. In males, the bladder neck is surrounded
by the prostrate inferiorly, where the urethra leaves the bladder. The fascia endopelvina
connects the bladder to the pelvic wall. This fascial attachment is strengthened
by a few muscular fibres anteriorly and posteriorly. The ureters and urethral openings
outline a triangular region, the trigonum vesicae, at the base of the bladder. The
orifices of the ureters are places at the posterolateral angles of the trigonum
vesicaea while the internal urethral orifice is placed at its apex. The arteries
supplying the bladder are the superior, middle and inferior vesical arteries, and
the obturator and gluteal arteries. The venous plexus from the urinary bladder drains
into the hypogastric veins. The innervation of the bladder arises from the third
and fourth sacral nerves and hypogastric plexus.1,2
Bladder Wall
The four layers (fig 2) of the bladder wall are the serous, muscular, submucous
and mucous. The serous layer (tunica serosa) is derived from the visceral peritoneum
and covers the superior surface and upper parts of the lateral surfaces. Fibrous
adventitia, a layer of areolar connective tissue, forms the superficial layer of
the posterior and anterior surfaces of the bladder wall. The tunica muscularis forms
the muscular layer with three layers of unstriped muscular fibres (inner longitudinal,
middle circular and outer longitudinal layers). The internal urethral sphincter
is formed by the circular muscular layer of the detrusor. The tela submucosa, a
layer of areolar tissue, connects the muscular and the mucous layers. The deepest
layer of mucosa is composed of transitional epithelium with an underlying lamina
propria. The mucous membrane is loosely attached to the muscular layer over the
greater part of the viscous except the trigonum vesicae.1,2
Structure of the Urothelium
The innermost layer of the bladder wall is formed by the urothelium( fig 3). This
highly specialised transitional epithelium, which extends from the renal pelvis
to the urethra, is organised into three distinct zones. The superficial apical layer
consists of polyhedral flattened cells (umbrella cells) with one to three nuclei.
The intermediate and basal cell layers are formed by large club shaped cells wedged
in between smaller spindle shaped cells. The suburothelial layer consists of nerve
endings, rich capillary network, several distinctive cells and myofibroblasts. The
mucous membrane of the bladder does not have any true glands.3,4
Transitional Epithelium: Effective barrier
The urothelium ( fig 4) serves primarily as a barrier in preventing bacterial and
crystal adherence to the bladder mucosa. It also prevents penetration of urinary
solutes into the bladder wall. In addition to its function as a protective barrier
to the underlying tissues, it also detects changes in physiological and chemical
stimuli. The terminally differentiated superficial urothelial cells, which display
molecular features, are primarily responsible for the barrier properties. They limit
permeability by the transcellular and paracellular routes. The tight-junction complexes,
specialised lipid molecules and uroplakin proteins in the superficial layer reduce
the movement of ions and solutes between cells. The inner mucosal lining of the
bladder is also densely coated with proteoglycans and glycosaminoglycan (GAG). This
GAG layer, which is also called the mucin layer, acts as a nonspecific antiadherence
factor by maintaining impermeability to infectious and toxic substances. The other
molecules detected in the normal urinary bladder mucosa are uroplakin, chondroitin
sulphate, tight junction molecule ZO-1 and cell adhesion molecule E-cadherin.4-7
However, local factors such as change in tissue pH, physical or chemical trauma,
or bacterial infection can alter the barrier function of the urothelium. This is
seen in conditions such as interstitial cystitis (IC) and spinal cord injury where
the underlying pathogenesis is the change in urothelial barrier function. The passage
of toxic substances leads to symptoms of urgency, frequency and painful micturition.
An increase in the levels of chemical mediators such as nitric oxide and adenosine
triphosphate (ATP) in certain pathological conditions alters epithelial function.4-7
Urothelium in IC
Interstitial disease is a disease of the urothelium. In this condition, the urothelium
fails to produce complete set of defence molecules normally synthesised. There is
an aberration in the differentiation programme with alteration in the synthesis
of proteoglycans, cell adhesion molecules, tight junction proteins and bacterial
defence molecules [Fig 5].4
The changes that occur in the bladder and the urothelium due to IC are as follows:
Thinning and denudation of the urothelium
Perivascular and peineural involvement
Upregulation of nerve growth factor
Loss of normal impermeability to urinary solutes
Increase in antiproliferative factor (inhibition of epithelial function)
Reduction in GDP51 (reduction in antibacterial defence mechanism)
Increase in the binding capacity of chondroitin sulphate
Increase in ATP and the stretch activated ATP releases [augment purinergic signalling]
4,6,8
