Urinary tract infection (UTI) is common in women, uncommon in men and of special importance in children. Recurrent infection causes considerable morbidity; if complicated, it can cause severe renal disease including end-stage renal failure. It is also a common source of lifethreatening Gram-negative septicaemia.
Infection is most often due to bacteria from the patient’s own bowel flora. Transfer to the urinary tract may be via the bloodstream, the lymphatics or by direct extension (e.g. from a vesicocolic fistula), but is most often via the ascending transurethral route For the latter route, three important steps are involved:
1 The periurethral area is heavily colonized with bacteria. This may be facilitated by the adhesion of bacteria to uroepithelial surfaces by pili or fimbriae present on their surface. Previous UTIs may also predispose to further colonization, initiating a vicious circle. Other factors involved are unclear, although gross lack of personal hygiene, the wearing of nappies or sanitary towels, local infection (e.g. vaginitis) and the use of bubble baths or chemicals in bath water have all been incriminated. 2 Bacteria are transferred along the urethra to the bladder. This step is facilitated by catheterization or sexual intercourse. Spontaneous transfer along the short female urethra is easy, while the longer male urethra protects against transfer of bacteria to the bladder; in addition, prostatic fluid has defensive bactericidal properties.
3 The most important step is the establishment and multiplication of bacteria within the bladder. Bladder urine is normally sterile, owing to bladder defence mechanisms that are the main protection against UTI. These include hydrokinetic and bladder mucosal factors. A low flow rate and infrequent and poor bladder emptying predispose to infection.
Mucosal defence mechanisms are poorly understood. The establishment of infection may be facilitatedby fimbriated bacteria adhering to the bladder uroepithelium or previous damage to this epithelium. Neither humoral nor cell-mediated immune mechanisms have been shown to play any part in maintaining the sterility of bladder urine.
The first phase in the development of UTI is the entry and establishment of bacteria within the bladder. Extension of infection up the ureters to the kidneys is relatively easy and is facilitated by vesicoureteric reflux and dilated hypotonic ureters. Once infection is established it can pass up or down the system quite readily.
UTI is commonly an isolated, never (or rarely) repeated event At least 50% of women will experience an episode of ‘cystitis’ at some time in their lives. Although often unpleasant, such single episodes of UTI rarely result in significant kidney damage. Recurrent or persistent infections are much more important. Complicated versus uncomplicated infection.
It is important to distinguish between UTI occurring in patients with:
FUNCTIONALLY NORMAL URINARY TRACTS (with normal excretion urography). Here, persistent or recurrent infection rarely results in serious kidney damage (uncomplicated UTI).
ABNORMAL URINARY TRACTS (e.g. with stones) or associated diseases (e.g. diabetes mellitus) which themselves cause kidney damage may be made worse with infection (complicated UTI). UTI, particularly with Proteus, may predispose to stone formation. The combination of infection and obstruction results in severe, sometimes rapid, kidney damage (obstructive pyonephrosis) and is an important cause of Gramnegative septicaemia.
Chronic pyelonephritis (also called atrophic pyelonephritis or reflux nephropathy) is now known to result from a combination of:
• Vesicoureteric reflux, and
• Infection acquired in infancy or early childhood
Normally the vesicoureteric junction acts as a one-way valve urine entering the bladder from above; the ureter is shut off during bladder contraction, thus preventing reflux of urine. In some infants and children- possibly even in utero-this valve mechanism is incompetent, bladder voiding being associated with variable reflux of a jet of urine up the ureter. A secondary consequence is incomplete bladder emptying, as refluxed urine returns to the bladder after voiding. This latter event predisposes to infection, and the reflux of infected urine leads to kidney damage. Typically there is papillary damage, interstitial nephritis and cortical scarring in areas adjacent to ‘clubbed calyces’. Diagnosis is based on excretion urography, which shows irregular renal outlines, clubbed calyces and a variable reduction in renal size. Reflux is confirmed by MCU.
The condition may be unilateral or bilateral and affect all or part of the kidney .
Reflux usually ceases around puberty with growth of the bladder base. Damage already done persists and progressive renal fibrosis and further loss of function occurs in severe cases even though there is no further infection. This condition does not develop in the absence of reflux and does not begin in adult life. It is therefore important to reassure adult females with bacteriuria and a normal urogram that kidney damage due to reflux nephropathy will not develop. Chronic pyelonephritis acquired in infancy predisposes to hypertension in later life and, if severe, is a relatively common cause of end-stage renalfailure in childhood or adult life. Early detection and treatment of infection, with or without ureteral reimplantation to create a competent valve, can prevent further scarring and allow normal growth of the kidneys. Reinfection versus relapsing infection When UTI is recurrent it is important to distinguish between relapse and reinfection. Relapse is diagnosed by recurrence of bacteriuria with the same organism within 7 days of treatment and implies failure to eradicate infection . It usually occurs in conditions in which it is difficult to eradicate the bacteria, e.g. stones, scarred kidneys, polycystic disease or bacterial prostatitis.
By contrast, in reinfection bacteriuria is absent after treatment for at least 14 days, usually longer, followed byrecurrence of infection with the same or different organisms. This is not due to failure to eradicate infection, but is the result of rein vasion of a susceptible tract with new organisms. Approximately 80% of recurrent infections are due to reinfection.
SYMPTOMS AND SIGNS
The most typical symptoms of UTI are:
• Frequency of micturition by day and night
• Painful voiding (dysuria)
• Suprapubic pain and tenderness
• Smelly urine
These symptoms relate to bladder and urethral inflammation, commonly called ‘cystitis’, and suggest lower urinary tract infection. Loin pain and tenderness, with fever and systemic upset, suggest extension of the infection to the pelvis and kidney, known as pyelitis or pyelonephritis. However, localization of the site of infection on the basis of symptoms alone is unreliable.
UTI may also be present with minimal or no symptoms or may be associated with atypical symptoms such as abdominal pain, fever or haematuria in the absence of frequency or dysuria. In small children, who cannot complain of dysuria, symptoms are often ‘atypical’. The possibility of UTI must always be considered in the retful, febrile sick child who fails to thrive.
Abacteriuric frequency or dysuria (‘urethral syndrome’)
Symptoms of frequency and/or dysuria are not synonymous with UTI and 50% of symptomatic young women may have no demonstrable bacteriuria. Alternative causes include postcoital bladder trauma, vaginitis, atrophic vaginitis or urethritis in the elderly, and interstitial cystitis (Hunner’s ulcer).
Interstitial cystitis is an uncommon but distressing complaint, most often affecting women over the age of 40 years. It presents with frequency, dysuria and often severe suprapubic pain. Urine cultures are sterile. Cystoscopy shows typical inflammatory changes with ulceration of the bladder base. The cause is unclear but it is commonly thought to be an autoimmune disorder. Various treatments are advocated with variable success. These include oral prednisolone therapy, bladder instillation of sodium cromoglycate and bladder stretching under anaesthesia.
Careful history-taking will identify a group with predominant frequency and passage of small volumes of urine who have ‘irritable bladders’, possibly consequent on previous UTI or conditioned by psychosexual factors. Such patients must be distinguished from those with frequency due to polyuria. Repeated courses of antibiotics in patients with abacteriuric frequency or dysuria are quite inappropriate and detract from identifying the true nature of the problem.