Analysis of Smooth Muscle and Collagen Subtypes in the Normal Newborn and Bladder Exstrophy Patient

  • Benjamin R. Lee
  • Elizabeth J. Perlman
  • Alan W. Partin
  • Robert D. Jeffs
  • John P. Gearhart



Many patients who undergo newborn bladder exstrophy closure, subsequent epispadias repair and later bladder neck reconstruction become completely continent, yet complications can occur. After a successful initial exstrophy closure and later epispadias repair, some patients may fail to gain sufficient capacity for bladder neck reconstruction. Others may fail to gain satisfactory capacity and continence after bladder neck reconstruction. In an attempt to understand the pathogenesis of these failures, the authors first compared bladder biopsies from normal neonatal bladders to newborn exstrophy bladders.

Materials and Methods

Bladder biopsies were taken from midline of the bladder wall just above the base of the trigone in twelve newborn exstrophy patients and compared to bladder sections from nine expired neonates. All bladder specimens were stained with monoclonal antibodies against Types I, III or IV collagen. A subset were further stained with Masson’s Trichrome to define the extracellular matrix. All specimens were then analyzed using a color digital image analysis system.


On initial examination of the extracellular matrix, there was an increase in colla?gen:smooth muscle ratio from 0.38 in controls to 1.2 in newborn exstrophy patients. This ratio was composed of both an increase in collagen as well as a decrease in smooth muscle. The collagen component of the extracellular matrix was then further defined to quantitate how much of each collagen type (I, III & IV) was being deposited.

The authors then examined the ratio of collagen type to total collagen sampled. Compared to control bladders, there was not a statistical difference in the amount of types I or IV in the newborn exstrophy bladder at time of initial closure. Interestingly however, there was a three fold increase in type III collagen, from 0.14+/−.05 to 0.46 +/−0.2 (p≪0.001) in the neonatal control bladders vs. newborn exstrophy bladders, respectively.


This alteration in collagen makeup may represent an earlier developmental stage of the exstrophied bladder at birth which then remodels and changes after successful initial closure. Further studies are underway to examine the collagen composition of bladders at the time of bladder neck reconstruction and failed closures as well as those undergoing bladder augmentation.


Bladder Neck Bladder Smooth Muscle Exstrophy Bladder Bladder Biopsy Bladder Calculus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gearhart JP: Failed bladder exstrophy repair - evaluation and management. Urol. Clin. North Amer. 18: 4, 1991.Google Scholar
  2. 2.
    Gearhart JP, Peppas DS and Jeffs RD. The failed exstrophy closure: strategy for management. Brit J Urol. 71: 217–22, 1993.PubMedCrossRefGoogle Scholar
  3. 3.
    Susset JG, Servot-viguier D, Lamy F, Madernas P, and Black R. Collagen in 155 human bladders. Invest. Urol. 16 (3): 204–206, 1978.PubMedGoogle Scholar
  4. 4.
    Baskin L, Howard PS and Macarak E. Effect of physical forces on bladder smooth muscle and urothelium. J Urol. 150: 601–607, 1993.PubMedGoogle Scholar
  5. 5.
    Landau EH, Jayanthi VR, Churchill BM, Shapiro E, Gilmour RF, Khoury AE, Macarak EJ, McLorie GA, Steckler RE and Kogan BA. Loss of elasticity in dysfunctional bladders: Urodynamic and histochemical correlation. J Urol., 152: 702–705, 1994.PubMedGoogle Scholar
  6. 6.
    Kim KM, Kogan BA, Massad CA and Huang YC. Collagen and elastin in the normal fetal bladder. J Urol. 146: 524–527, 1991.PubMedGoogle Scholar
  7. 7.
    Peppas DS, Tchetgen MB, Jeffs RD and Gearhart JP. A quantitative histological analysis of the bladder in classical bladder exstrophy in various stages of reconstruction utilizing color morphometry. Submitted for publication, 1996.Google Scholar
  8. 8.
    Macarak EJ, Howard PS and Lally ET. Production and characterization of a monoclonal antibody to human type III collagen. J Histo Cyto. 34 (8): 1003–1011, 1986.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Benjamin R. Lee
    • 1
  • Elizabeth J. Perlman
    • 1
  • Alan W. Partin
    • 1
  • Robert D. Jeffs
    • 1
  • John P. Gearhart
    • 1
    • 2
  1. 1.Departments of Urology and PathologyThe Johns Hopkins School of MedicineBaltimoreUSA
  2. 2.Division of Pediatric Urology—Marburg 149, The James Buchanan Brady Urological InstituteThe Johns Hopkins HospitalBaltimoreUSA

Personalised recommendations