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Relevant Anatomy and Physiology

Anatomy of the urinary bladder [vesica urinaria]

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

Urniary Tract

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

Urniary Tract

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

Urniary Tract

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

Urniary Tract

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

Points of aberration in the urothelium in IC

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

  1. Marieb EN, Hoehn K. The Urinary System. In: Marieb EN, Hoehn K, eds. Human Anatomy & Physiology. 7 ed. San Francisco, CA: Pearson Education, Inc; 2007:997-1034.
  2. Tortora GJ, Derrickson B. The Urinary system. In: Tortora GJ, Derrickson B, eds. Principles of anatomy & physiology. 12 ed. Hoboken, NJ: John Wiley & Sons, Inc; 2009:1018-1061.
  3. Fry Ch, Roosen N. Urothelial targets in the overactive bladder. J Urol Urogynakol. 2007;14(1):19-22.
  4. Hurst RE, Moldwin RM, Mulholland SG. Bladder defense molecules, urothelial differentiation, urinary biomarkers, and interstitial cystitis. Urology. 2007;69(4A):17-23.
  5. Birder LA. More than just a barrier: urothelium as a drug target for urinary bladder pain. Am J Physiol Renal Physiol. 2005;289:F489-F495.
  6. Birder LA, de Groat WC. Mechanisms of disease: Involvement of the urothelium in bladder dysfunction. Nat Clin Pract Urol. 2007;4(1):46-54.
  7. Southgate J, Varley CL, Garthwaite MAE, et al. Differential potential of urothelium from patients wiht benign bladder dysfunction. BJU Int. 2007;99(6):1506-1516.