1. A healthy bladder and urethra
The yellow part is the urine and the pink area is the urothelium – the tissue lining of the bladder and parts of the urethra.
The urothelium is made up of epithelial cells – seen here with a purple cell nucleus.
2. Early phase of a urinary infection
The normal bladder is not sterile and contains at least 550 different species of bacteria. It has plenty of microbes – bacteria, fungi and viruses – swimming around in the urine but they are in comfortable balance with the body and not causing symptoms.
But some microbes are pathogens – bacteria that can cause infections or disease.
Bacilli are an example of one type of bacteria that can cause a urinary infection – they are shown here in green swimming in the urine.
3. Changes to the tissue lining of the bladder
The bacilli bacteria have changed form and have adopted the shape of round cocci – spherical, ovoid or round shape. They have penetrated down to the base of the urothelium and some have entered the cells. This is called intracellular colonisation.
When infection causing bacteria enter cells they go into a dormant state, similar to hibernation, and so do not divide. They are only affected by antibiotic attack when they start dividing, so while they are dormant they survive antibiotic treatments.
Here you can see the bacilli enter the epithelial cells.
4. The bladder becomes inflamed
The cells that have become colonised by the infection causing bacteria – in this case bacilli – send distress signals to the immune system, which causes an inflammatory response.
Blood vessels dilate up and cause the bladder wall to look red or inflamed. Some of these blood vessels might burst and leak blood into the urine which will be detected on dipstick analysis or microscopy.
Attracted by chemicals, called cytokines which are released by the infected cells, bacteria start to infiltrate the urothelium (the tissue lining of the bladder and parts of the urethra).
The white blood cells fail to detect a problem because the bacteria are hiding inside the epithelial cells. But the urothelial cells do detect a problem and this standoff results in chronic inflammation and pain.
This inflammation and pain can persist despite apparently ‘normal’ urine results. This is because standard tests look in the wrong place. The bacilli are safe, lying dormant inside the urothelial cells and not in the urine which is collected for tests.
Here you can see the bacilli inside the epithelial cells and the white blood cells starting to arrive – show in red.
5. Persisting inflammation causes the urothelium to thicken
All epithelial tissue thickens when stressed in any way through a process called metaplasia.
The tissue lining the of bladder and parts of the thickens as it attempts to form a protective barrier. But it is not very effective – the microbes are already inside the cells.
Both inflammation and the increased number of urothelial cells thicken the wall of the epithelial tissue.
This thickening causes some obstruction which leads to the most sensitive symptom of infection – voiding. Voiding symptoms include hesitancy to pee, a reduced stream, intermittency – stopping and starting, terminal dribbling, post dribbling and double voiding – feeling like you need to go back pee again straight after going.
The thickened and inflamed bladder wall reduces bladder capacity. Inflammatory chemicals can cause the bladder muscle to contract inappropriately. Both cause symptoms like needing to go more frequently, more urgently or urge incontinence – a sudden and strong urge to go.
Here you can see the bladder wall thickened and inflamed.
6. Bacteria that cause disease get into biofilm
Biofilms – groups of microbes which come together in a jelly and stick to the inside or outside of cells – are a normal part of our body. They are found all over our body.
But when bacteria that can cause infection and disease get into a biofilm, these bacteria stop dividing and become unsusceptible to antibiotic attack. The now dormant pathogenic bacteria irritate the cells and cause inflammation.
From time to time the pathogenic bacteria can wake up, divide vigorously, burst out the cell and set up fresh infection in new cells.
The white cell count is the best marker of urinary infection but it needs to be done straight away on a fresh, unspun, unstained specimen of urine examined using a microscope and a haemocytometer counting chamber.
Here, you can see white cells in the urine – shown in purple. The urinary red blood cells which sometimes accompany inflammation of the bladder are shown in red. The microbes – shown in green – can be seen forming biofilms on the surface of cells and inside the cells.
7. Cells are infected
Pathogen bacteria escape from shed cells, divide and infect new, fresh cells at the base of the bladder lining.
The body’s natural immune system responds to the infection by shedding the cells. It’s the most effective way of getting rid of the infection.
But the bacteria have detected that they are inside a cell that is dying. They must escape, by waking up and dividing vigorously to create a microbial swarm that bursts out of the cell into the urine.
Here the bacilli bacteria have woken up and are bursting out of the cells into the urine. Healthy cells at the base of the urothelium are colonised by the bad bacteria. The infection spreads.
Find out more
- What is chronic UTI?
- Why are my tests negative?
- Support for people with chronic urinary tract infection