Figure 5 illustrates a further stage in the evolution of the persisting inflammation. The urothelium thickens. All epithelial tissue will thicken, through a process called metaplasia, when stressed in any way. The skin of the feet shows this through the formation of corns caused by poorly fitting shoes. The purpose of the thickening is an attempt to form a protective barrier; but it is not very effective since the offending microbes are inside the cells. Given this occurrence, it will take longer for a cell at the base to reach the surface.
This thickening of the cellular part of the urothelium contradicts the unproven ideas about GAG layers and drugs that encourage replacement of the GAG layer. There is no evidence for GAG layer deficiency, instead the urothelium is laying down a barrier made of many cells and vastly thicker than a GAG layers or any other surface protein. It is no surprise that a 2016 analysis of 36 randomised controlled trials, evaluating 1,822 participants conducted on the use of bladder instillations showed that they are no better than placebo. There is no coherent pathophysiological reason for why they should work.
Some years ago there was a flurry of interest in bladder wall thickness detected by ultrasound in patients with lower urinary tract symptoms. Eventually this observation was found not to correlate with urodynamic study data from cystometrograms and interest waned. This was a pity because the bladder wall thickness may carry a more relevant message than people assume. However, it supports the experience, demonstrated in clinical trials, that urodynamic studies shed no light on this condition and should have no role to play.
The inflammation and the increased number of urothelial cells will also thicken the wall of the urethra. This causes a degree of obstruction and thus we find that the most sensitive symptoms of infection are the voiding symptoms: Hesitancy, reduced stream, intermittency, terminal dribbling, post-micturition dribbling and double voiding. Some surgeons recommend urethral dilation as a treatment, but that is to confuse cause and effect: The voiding problem is not causing the infection it is the other way round. A similar muddle influences concerns about incomplete bladder emptying; the inflammation leads to a degree of urinary retention that can be resolved by treating the infection and not by using intermittent catheterisation. There is no good reason why a volume of urine left behind in the bladder after voiding should cause infection. Some patients with severe attacks of infection can develop acute urinary retention.
The thickened and inflamed bladder wall will reduce the bladder capacity and the inflammatory chemicals may cause the bladder muscle to contract inappropriately leading to frequency, urgency and urge incontinence. Pain may also play a role in a low bladder capacity. Stretching the bladder by hydro distension or cystodistension is not going to help this situation at all but it will surely make the bladder wall bleed. This figure shows red blood cells in the urine which can be a manifestation of chronic inflammation anyway.
The published literature shows no evidence of benefit from cystodistension or urethral dilation. That is not so surprising since stretching was never thought to help with an inflammatory infiltration causing metaplasia.
The metaplasia of the bladder can be seen on cystoscopy where plaques and fronds on the bladder wall, notably at the trigone, are evident. Some surgeons cauterise such lesions. Why should that help? If you want to burn away the chronic infection you would really have to set fire to the whole bladder. How will cauterised bladder urothelium repair in tissue that is harbouring a chronic infection?