Congenital abnormalities of the lower urinary tract of children adversely affect bladder function, both immediately and throughout development, and can result in renal failure. Such patients with pathological bladder states often require reconstructive surgery in an attempt to restore lower urinary tract function. However, it is unknown if there are functional defects to the musculature of the bladder - the detrusor smooth muscle. The aim was to examine the functional properties of human paediatric detrusor in normal patients and those with pathological bladder conditions. Full thickness bladder specimens were taken from pathological bladder conditions such as posterior urethral valves, neuropathic bladder, and bladder exstrophy. Normal tissue was obtained from those with urachal anomalies or from those undergoing ureteric reimplantation procedures. Ethical committee approval and patient consent were obtained at the time of surgery at Great Ormond Street Hospital. The bladder contractile properties were characterised by in vitro myopathy and electrical field stimulation in all patient groups. The histological properties were also examined in these groups. Additionally, with bladder exstrophy samples the viscoelastic properties of the tissue was measured by passive stretch studies to determine their contribution to the overall mechanical properties. Finally, intracellular Ca2+ responses in single detrusor muscle cells to agonist stimulation were measured by epifluorecence microscopy. Nerve and agonist-mediated contraction amplitude was significantly less in samples from patients with pathological bladders compared to those with normal bladder. Histological evaluation revealed an increase in the connective tissue to smooth muscle ratio in pathological bladders. In bladder exstrophy the tissue was mechanically stiffer but the single cell responses were similar to the normal detrusor responses following agonist application. The data shows that detrusor from paediatric patients with pathological bladders exhibited reduced contractility, whether elicited by excitatory nerves or agonist application. Functional innervation was reduced in pathological bladders and the pattern of excitatory neurotransmitter release was altered.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:626325 |
| Date | January 2013 |
| Creators | Johal, N. S. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1403222/ |
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