BASIC SCIENCE

The pathophysiology of anomalies, renal calculi or prostate enlargement; or the presence

of a foreign body e such as a urethral or suprapubic catheter.2

urinary tract infections

Practical interpretations of commonly used terms2e4
Chloe Walsh Cystitis: bladder inflammation. Clinical syndrome of dysuria,
Tim Collyns urinary frequency and urgency, which may be accompanied by
supra-pubic tenderness. The commonest cause of the inflam-
mation is infection, but not exclusively. These symptoms and
Abstract signs can be termed those of the ‘lower urinary tract’, and the
Urinary tract infections are amongst the most bacterial infections. They infection has not ascended beyond the bladder.
can occur in either an uncomplicated host setting, where there is no
underlying structural or functional abnormality of the patient’s genito- Urethritis: inflammation of urethra, usually due to infection.
urinary tract, or complicated, where there is. For the latter, common Associated symptoms may mimic those of cystitis. Infective
predisposing factors are the presence of a foreign body, including uri- causes, such as Neisseria gonorrhoeae or Chlamydia trachomatis,
nary catheter, or disruption of normal urinary flow by obstruction or are usually acquired during sexual contact and do not ascend to
retention. Bacteria vary widely in their ability to successfully invade the bladder, so although the urethra is normally the final
the urinary tract; the vast majority of such infections being due to a passageway for urine from the body (and the primary route for
small number of species. The route is usually ascension from the ure- organisms to gain access to the bladder and beyond), specific
thra. Certain uropathogenic strains of Escherichia coli are the most urethral infections are not usually included in the term UTI.
proficient as measured by their frequency of being the identified
cause. Such strains display a number of virulence factors which Acute urethral syndrome: the typical symptoms of cystitis in the
enable them to occupy this niche e which with increasing understand- absence of a ‘significant’ bacteriuria. Some of these patients still
ing, may promote different methods of treating. Other species are have bladder involvement but with relatively low pathogen
often implicated only in the presence of an underlying urological ab- counts, whilst in a proportion, the inflammation and associated
normality. The presence of a urinary catheter, or other urine drainage uropathogen (usually Escherichia coli) is genuinely limited to the
device, provides a ready scaffold for organisms to develop a biofilm, urethra. (NB: these symptoms can also be caused by sexually
which in turn shields them from being eradicated successfully. Renal transmitted pathogens.)
calculi similarly can be linked to biofilm production.
Acute pyelonephritis: this describes the symptoms and signs
Keywords Biofilm; catheter; cystitis; Escherichia coli; pyelonephritis;
which are generated when a kidney (the ‘upper urinary tract’) is
urease
infected e such as flank pain and tenderness, and pyrexia. Non-
infectious causes, such as renal stone or infarction, can mimic
this presentation. Upper urinary tract involvement is also usually
Introduction
accompanied by lower urinary tract symptoms and signs.
Urinary tract infection (UTI) is one of the most common bacterial
infections, particularly affecting women. Up to half of women Uncomplicated UTI: infection in a normal urinary tract, both
will suffer at least one episode of UTI in their lifetime and one in structurally and neurologically.
four of these women will develop a recurrence.1,2 Signs and
symptoms differ according to the site of infection; upper UTI Complicated UTI: symptomatic infection of the bladder or kid-
(pyelonephritis) classically presents with fever and flank pain neys, in the presence of a structural or functional abnormality of
whilst lower UTI (cystitis) typically presents with some or all of the genitourinary tract. Common factors include presence of a
the following: dysuria, frequency, haematuria and suprapubic foreign body (e.g. in-dwelling urinary catheter or other drainage
tenderness. Here we examine the mechanism of UTIs and the device or renal calculus); disruption of normal urinary flow
host and microbiological factors associated with these infections. (e.g. by obstruction or urinary retention) or immunosuppression.
Key predisposing host factors involved in complicated UTIs are Infection in children or men should be assumed to be compli-
either obstruction of normal urinary flow, such as by congenital cated unless confirmed to the contrary.

Recurrent urinary tract infection: a further symptomatic

episode following previous resolution of a UTI. It can reflect
either re-infection or bacterial persistence. Significant recurrent
UTI is defined as three or more episodes of UTI within a 12-
Chloe Walsh MA MB BChir MRCP is a Specialist Joint Medical
Microbiology and Infectious Diseases Registrar at the Leeds month period.5
Teaching Hospitals Trust, Leeds, UK. Conflicts of interest: none
declared. Significant bacteriuria: bacteriuria is the presence of bacteria in
urine. Urine in the bladder is normally sterile e however, low
Tim Collyns MA MB BChir FRCPath is a Consultant Medical
Microbiologist and the Lead Infection Control Doctor at the Leeds numbers of organisms in a urine sample may be due to
Teaching Hospitals Trust, Leeds, UK. Conflicts of interest: none contamination by normal anterior urethral flora. A significant
declared. bacteriuria is one where the bacterial count is sufficiently great to

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 BASIC SCIENCE

indicate a genuine bladder bacteriuria. Historically, this has been peri-urethral area.7 Once within the bladder, bacteria may then
defined as a count 105 colony forming units (cfu) of the ‘same’ multiply and ascend the ureters to cause upper UTI.
organism per mL of urine in two consecutive clean-catch, voided
urine samples in women. In men, a single sample of clean-catch Haematogenous infection
voided urine with a count of 105 of one species is sufficient. It is Less commonly, upper UTI can be a result of haematogenous
important to recognize that symptomatic infections can still be spread of bacteria, for example in prolonged bacteraemia, often
associated with lower counts e notably if a pure growth of a associated with a deep source of infection such as endocarditis.
well-recognized uropathogen. Conversely, significant bacteriuria Direct animal studies support this, showing that intravenous
in the absence of symptoms often does not require treatment (see injection of Staphylococcus aureus can result in pyelonephritis.8
below). For samples derived via a urinary catheter, a lower However, it is more difficult to produce pyelonephritis in
threshold may be applicable due to the reduced risk of contam- similar models with Gram-negative bacteria, suggesting that this
ination. For practical laboratory testing purposes, 103 cfu/mL is not the common route of infection for most pathogens.
of 1 bacterial species in a single catheter-derived sample is a
useful cut-off. Host factors in urinary tract infections
Women
Asymptomatic bacteriuria: bacteria may be isolated from urine UTIs are more common in women because of their anatomy; the
at significant counts, in the absence of any accompanying shorter urethra and the relative proximity of the urethra to the
symptoms. This is more common with increasing age e being anus. Several other factors have also been shown to increase the
reported to be present in a tenth of men and a fifth of women risk of UTI in women: particularly sexual intercourse and the use
over the age of 65.2 Unlike in younger adults, where significant of spermicide,9 which is thought to affect the vaginal microbial
bacteriuria is 30 times more common in women than men, there flora resulting in a reduction in lactobacilli allowing for an
is a progressive decrease in the ratio of women to men with this increased proportion of potentially pathogenic Gram negative
phenomenon with increasing age. Factors which make older bacteria, such as E. coli to colonize the genital tract.10 Post-
men more prone to bacteriuria include reduced bactericidal ac- menopausal women are particularly prone to recurrent UTI.
tivity of prostatic secretions, and prostatic enlargement leading Reduced oestrogen levels increase the risk of vaginal atrophy,
to urinary retention. In both genders, there is a high rate of which results in vaginal dryness and increased pH, which in turn
spontaneous clearance of bacteriuria e followed by subsequent alters the vaginal microbial flora, reducing the proportion of
reinfection. Antimicrobial treatment of asymptomatic bacteri- (‘protective’) lactobacilli.11 In addition, low oestrogen levels are
uria in adults is rarely warranted; and is more likely to be associated with post-voiding residual urine in the bladder, which
associated with patient ‘harm’ than benefit and so should be is a further risk factor for UTI.
avoided. This includes people of either gender over the age of
65; catheterized individuals; and younger women who are not Genetic factors
pregnant. The two groups of adult patients with asymptomatic Recurrent UTIs in women are more common in those with a
bacteriuria in whom treatment is recommended are pregnant family history, suggesting a genetic pre-disposition. Host factors
women and those prior to a urological procedure where mucosal to protect against UTI include physical barriers (such as uni-
bleeding is anticipated. directional urine flow), proteins that hinder bacterial adhesion
and the cells of the innate immune system, including neutrophils.
Pyuria: presence of a raised count of polymorphonuclear leu- Polymorphisms of various genes have been found to be associ-
kocytes (PMLs) in urine (e.g. 10 PMLs per mm3 of urine), but ated with recurrent UTI.12 CXCR1 and 2 are IL-8 receptors that
unit of measurement and definition vary with counting method play a role in neutrophil recruitment and reduction in CXCR1
used. This is indicative of an inflammatory response in the uri- expression has been associated with recurrent UTI in children.12
nary tract e however, it is neither specific for infection, nor for CXCR2 levels have been shown to be lower in women with
symptoms in the presence of a bacteriuria. Ninety per cent of recurrent UTI compared to controls.13
asymptomatic elderly institutionalized patients with a bacteriuria
will also have a pyuria. Pyuria in the absence of bacteriuria can Structural abnormalities
be associated with other pathologies, such as renal stone disease, Certain renal tract pathologies increase the risk of recurrent UTI.
malignancy and tuberculosis of the renal tract, which should be Conditions resulting in a residual volume of urine post voiding,
considered depending on the clinical scenario. for example neurogenic bladder, reduce the protection of the uni-
directional flow of urine and so increase the risk of UTI. The
Mechanism of infection same applies to the increased risk of UTI associated with vesico-
ureteric reflux. Renal stone disease is also associated with UTI.
Ascending infection
The foreign material provides a surface for bacteria to form a
The most common route of infection is ascension of bacteria
biofilm. This prevents bacteria from being easily removed from
from the urethra to the bladder. Early animal studies supported
the urinary tract by the flow of urine and renders the bacteria
this, showing that if bacteria were directly instilled into the
more difficult to eradicate by the host immune response.
bladder, and one ureter was ligated, the unligated kidney was
more likely to develop pyelonephritis.6 The most common bac- Catheterization
terial causes of UTI are the same bacteria that colonize the gut Indwelling catheters are well known to increase the risk of
and they enter the urinary tract following colonization of the recurrent UTI, by enabling bacteria to form biofilms, providing a

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 BASIC SCIENCE

reservoir of potential pathogens that are in contact with the containing receptors, such as uroplakin, on the latter.2,15 This
bladder. Almost all catheters in situ for four or more weeks are binding can lead to host cell shedding and bacterial invasion of
colonized by bacteria.14 In addition, if the biofilms formed are deeper cell layers of the bladder wall. The expression of the
crystalline, they can block the flow of urine, exacerbating the fimbriae can be modulated by the organism e such that they
problem. may be present at the start of a UTI but be down-regulated later
on when their ongoing presence is no longer to the bacteria’s
Microbiological factors in urinary tract infections advantage.2 Co-trimoxazole has been shown to reduce the syn-
thesis and function of type I fimbriae at concentrations well
The urinary tract can potentially be infected by a very wide range
below the concentration required to inhibit bacterial growth,
of organisms e including viruses, bacteria, fungi and parasites.
which may partly explain its efficacy as prophylactic agent.
However, in reality, a limited number of bacterial species are the
Another adhesin is found on P fimbriae. These fimbriae have the
cause of the vast majority of UTIs, with usually only a single
ability to bind to globoseries glycosphingolipid receptors that are
species involved in any one infection.2 The relative percentages
contained in the P blood group antigen complex (hence name)
vary with underlying host factors e i.e. whether uncomplicated
present on red blood cells, but also on renal uroepithelial cells of
or complicated. The archetypal species is E. coli (E. coli), which
approximately 99% of the population. Its pathogenic importance
tops both lists (Table 1). The virulence factors enabling an or-
is highlighted by the finding that uncomplicated upper UTI due to
ganism to establish an infection vary between, and within, spe-
E coli is virtually never seen in the other 1%.
cies. Organisms capable of causing uncomplicated UTIs (i.e.
Various other adhesins have been identified on UPEC; such as
effectively where there are not predisposing host features to
on M, G and S fimbriae.2,15 E coli strains that carry Dr adhesins
‘assist’ the bacteria) are the ones that usually display the greater
can be associated with persistence e either in the kidney or
specific uro-virulence factors. Some of these species, and char-
within bladder epithelial cells. Infections by such organisms may
acteristics of associated infections, are considered below.
then give rise to symptomatic relapses following a course of
Gram-negative bacteria seemingly effective antibiotic therapy.
Escherichia coli: the most common cause of all UTIs is E. coli e Iron is an essential element for virtually all organisms, acting
but not all strains of this bacterium are equal in their ability to as a co-factor for some vital enzymes. The bladder is an iron-poor
infect successfully the urinary tract. The natural reservoir for the environment and so successful UPEC strains have various side-
species is the human gastrointestinal tract, where it is the most rophores e proteins which scavenge this element, such as aer-
common facultative anaerobe present. Uropathogenic E. coli obactin. UPEC can also produce toxins, such as haemolysin and
(UPEC) strains have several virulence factors, which increase cytotoxic necrotizing factor 1.2,15 UPEC can also downregulate
their ability to invade the urinary tract. Some of the features the host’s acute immune response, by suppressing the trans-
which enable strains to cause urinary tract infections also pro- epithelial movement of neutrophils and reducing their produc-
mote their ability to cause other infections outside the gut, and so tion of antibacterial reactive oxygen species.
a broader term is extra-intestinal pathogenic E coli (ExPEC).2 Some E coli strains associated with asymptomatic bacteriuria
Fimbriae (from the Latin for thread), also known as pili (from have been shown to have a loss of expression of various func-
the Latin for hair), are surface nanofilaments which may extend tional virulence genes.
for several micrometres in length from the bacterial cell. They Klebsiella pneumoniae: K. pneumoniae is second only to E.
serve a variety of functions, including allowing bacterial adher- coli in causing bloodstream infections (bacteraemias), associated
ence to host cells, aggregation of bacteria and exchange of ge- with a UTI.2 This species can also produce various types of
netic material. The presence of ‘type I’ fimbriae has been shown fimbriae, including type 1.2,15 However, K. pneumoniae also
to be a key factor in enabling bacterial binding to superficial produces a polysaccharide capsule surrounding its outer cell
bladder uroepithelial cells, due to the presence of mannose membrane, of which there are over 70 antigenic types. The
capsule inhibits phagocytosis, and its’ presence has been shown
to have role in UTIs in animal models. Klebsiella species also
produce a urease, the pathogenic role of which is described
Common causes of UTI (uncomplicated and complicated) below.
in descending order of prevalence2,15 Proteus mirabilis: there are various species of Proteus, but the
most common ones causing human infections are Proteus mir-
Uncomplicated UTI Complicated UTI
abilis and Proteus vulgaris. P. mirabilis may be the cause of an
Escherichia coli Escherichia coli uncomplicated UTI, but more commonly causes infection in the
Klebsiella pneumonia Enterococcus species setting of an abnormal urinary tract, including if an indwelling
Staphylococcus saprophyticus Klebsiella pneumonia catheter is present. P. mirabilis may also possess a variety of
Enterococcus faecalis Candida species fimbriae, the most important of which in the setting of UTIs, are
Streptococcus agalactiae Staphylococcus aureus the MR/P fimbriae, which have been shown to be associated
(Group B Streptococcus) Proteus mirabilis with bladder colonization/infection in the murine model and
Proteus mirabilis Pseudomonas aeruginosa whose production can be regulated similar to type 1 fimbriae in
Pseudomonas aeruginosa Streptococcus agalactiae E. coli.2,15 P. mirabilis also produces a potent urease enzyme,
Staphylococcus aureus (Group B Streptococcus) which hydrolyses urea into carbon dioxide and ammonia. This,
in turn, raises the urine pH, causing the precipitation of struvite,
Table 1 magnesium ammonium phosphate, which in turn agglomerates

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 BASIC SCIENCE

to form a renal calculus.16 Viable bacteria may be embedded the face of osmotic and pH changes.2,15 UTIs due to this organism
within the crystal, which can then act as a nidus for recurrent have been found to be more common in late summer and
infections. Therefore, recurrent isolation of P. mirabilis should autumn; and may be concomitant with vaginal candidiasis.2
raise the suspicion of renal stones. Of note, there is likely to be a Other coagulase-negative Staphylococci: genuine infections
loss of white cells in urine, with the increased alkalinity, leading due to these organisms are almost entirely restricted to hospi-
to a lack of an accompanying pyuria. Other organisms can also talized patients with underlying urological issue(s) e usually
produce ureases, such as Klebsiella, Pseudomonas, Staphylo- with an indwelling catheter in place.2 90% of these infections are
coccus and Corynebacterium urealyticum.2,15 In addition to the due to Staphylococcus epidermidis. This organism, although
potency and amount of urease produced, the host’s inflammatory being of very low virulence in an otherwise healthy host, is well-
response to the presence of the infecting organism may also have adapted to adhering to, and forming biofilm on, foreign material
a role in stone generation; with the more exuberant response e such as a urinary catheter. It can produce autolysins which
having been shown to be more likely to be associated with stone bind directly to plastic and other compounds; and bacterial
formation in a rat model.17 products such as accumulation associated protein, Bap homo-
logue protein, polysaccharide intercellular adhesion and extra-
Other Enterobacteriaceae: species such as Enterobacter, Serra- cellular DNA contribute to biofilm formation.2
tia, or Citrobacter rarely cause UTIs in normal hosts e but not
uncommonly cause healthcare associated UTIs e notably in the Enterococci: Enterococci cause fewer than 5% of uncomplicated
presence of an indwelling catheter.2 The commonly isolated UTIs. However, they are well-established as a cause of health-
species in these genera are intrinsically resistant to ampicillin care-associated infections, in the presence of a urinary catheter
and the first-generation cephalosporins, such as cephalexin or and/or other urological abnormality or procedure. They have
cephradine, due to a chromosomally encoded AmpC beta- intrinsic resistance to a number of commonly used antibiotics.
lactamase. The main two species involved in infections are Enterococcus
Pseudomonas aeruginosa, along with other pseudomonads, faecalis and Enterococcus faecium, the latter being intrinsically
are ubiquitous in diverse environments, such as water, soil and resistant to penicillins such as ampicillin or piperacillin.
plants. However, P. aeruginosa does not usually form a signifi- Enterococci are well-adapted to colonizing the human
cant portion of the normal resident microbial flora, the micro- gastrointestinal tract and receipt of antibiotics by the host, such
biome, in healthy hosts; such as in the gastro-intestinal or as a cephalosporin, can alter the balance in favour of entero-
vaginal tracts. P. aeruginosa usually causes urinary infections in coccal proliferation as they are naturally tolerant to various
a healthcare setting, often associated with a urinary catheter. It antimicrobial classes. Enterococci can produce various adhesins
rarely causes community ‘acquired’ infections, unless there is an and aggregation substances which establish and maintain bio-
underlying urological issue, such as obstruction, recent instru- films.2,15 Enterococci are of relatively low pathogenicity and may
mentation or neurogenic bladder. P. aeruginosa is intrinsically colonize catheters rather than causing symptomatic infection.
resistant to many commonly used antibiotics, such as trimetho- Similarly, their presence may prevent a more pathogenic species
prim, nitrofurantoin, co-amoxiclav, and most cephalosporins e from successfully invading the urinary tract e i.e. treatment of
which gives it a survival advantage over other potential patho- an asymptomatic enterococcal bacteriuria can be followed by a
gens in hospital. This organism has various virulence factors; symptomatic infection, due to a different organism.
including a well-developed quorum sensing (QS) pathway, Group B Streptococci (Streptococcus agalactiae): similar to
which enables communication between bacterial cells. QS is enterococci, Streptococcus agalactiae is very capable of colo-
involved in the establishment and control of biofilms.2,15 nizing the lower gastro-intestinal tract (10e25%) and in women,
also the genital area, (10e40%).2 Various factors have been
Gram-positive pathogens identified, which can increase female genital carriage, such as
Staphylococci: the staphylococcal species that cause UTIs can be increased sexual activity, diabetes and black ethnic origin. Group
divided into three e S. aureus, Staphylococcus saprophyticus and B streptococci can be associated with the full gamut of clinical
other coagulase-negative staphylococci. presentation from asymptomatic bacteriuria to urosepsis. If a
S. aureus: this organism has been described as the ‘prince of bacteriuria with Group B streptococci is identified during a
pathogens’ due to its array of virulence factors and success in pregnancy, then this is a marker of heavy genital colonization e
colonizing, and causing infections, in humans. However, it rarely and intra-partum prophylaxis is warranted to prevent invasive
causes uncomplicated UTIs. In the absence of a catheter, the infection in the neonate.
detection of S. aureus in urine may represent contamination by Corynebacterium urealyticum: Corynebacteria, ‘diphthe-
perineal flora; or be due to haematogenous spread, involving the roids’, are common skin commensal flora. This organism is no
kidneys, from a focus elsewhere resulting in ‘descending’ urinary exception, having been found to colonize the skin of over a third
tract involvement.2 Occasionally, the source may be the prostate. of hospitalized patients.2 However, unlike most other cor-
S. saprophyticus: this organism has a specific niche as a cause ynebacterial species, it is able to adhere to uroepithelial cells and
of UTIs e it is second only to E. coli in causing uncomplicated is a potent urease producer. It can cause chronic or recurrent
infections in sexually active, young women; however, it rarely UTIs, usually in patients with underlying predisposing factor(s)
causes infections in men or older women. It has a unique for a UTI. Due to the urease produced, it can cause ‘encrusted
adhesion protein, UafA, which facilitates its adhesion to uroepi- cystitis’, where there is chronic bladder mucosal inflammation
thelial cells. It produces urease, as well as having various with crystal deposits and surrounding erythema; or ‘encrusted
transport proteins, which enable it to survive, and multiply, in pyelitis’ if there is upper urinary tract abnormality.2

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 BASIC SCIENCE

Other pathogens and proliferate. As the lesions expand, the organisms are shed
Candida: Candida species are normal human commensal flora, into the renal tubules, involving the medulla. Here, the hyper-
and can be found harmlessly in the gastro-intestinal and female tonicity impedes macrophage function, allowing further
genital tracts. Candida spp. are also able to form biofilms on destructive organism proliferation. Sloughing of renal papillae
prosthetic surfaces and are commonly found in urine of patients may lead to caliceal, even ureteric, obstruction. The tubercle
with indwelling catheters without causing symptomatic infec- bacilluria may also lead to ureteral and bladder involvement.
tion.2 Disturbance of the natural balance of constituents, notably Patients with renal TB are often asymptomatic for some time, but
by antibiotics, enables Candida species to proliferate, which may then may present with urological complaints, such as dysuria,
then yield mucous membrane infections, such as vaginitis. In frequency, haematuria and back pain.2
women, urinary tract infection may then develop by extension;
whilst men may acquire urethral candidiasis after sexual contact Biofilms and catheters
with Candida vaginitis. Biofilms are multicellular microorganism communities,
enmeshed within a protective scaffold of extracellular material,
Viruses: a number of viruses have been linked to haemorrhagic including polysaccharides and DNA. Biofilm formation protects
cystitis or other urinary tract pathologies. Haemorrhagic cystitis the individual organisms within from the host’s immune response;
may be a benign self-limiting illness in children, presenting with as well as from other existential threats such as antibiotics. UPEC
gross haematuria which resolves in a few days; or following can form such bacterial communities within the uroepithelium,
renal or haemopoietic stem cell transplants (HSCT). Viruses and quiescent intracellular reservoirs can then act as niduses for
implicated include the BK virus and the adenovirus. BK virus recurrent infections. P. aeruginosa is able to establish a biofilm on
(BKV), a polyoma virus, is ubiquitous globally, and up to 90% of damaged bladder tissue, by various mechanisms, including
adults possess antibodies against it, having acquired the organ- quorum sensing to induce the production of rhamnolipids, which
ism asymptomatically as children.2 BKV exhibits tropism for cells change the hydrophobicity of the bacterial cell surface, and lectin
of the genito-urinary tract, including those of the renal tubular adhesins, both of which promote microcolony formation; coupled
epithelium, where it may remain latent. It does not cause disease with elastases and extracellular DNA.15
in immunocompetent hosts e although up to 20% of such in- Urinary catheters and other prosthetic devices are particularly
dividuals may shed the virus in urine. However, in immuno- ‘tempting’ targets for biofilm formation by microorganisms. The
compromised patients, it may reactivate. The virus is actually urease of P. mirabilis leads to the formation of crystals as
named after the initials of a renal transplant patient who devel- described above e which in turn are trapped by extracellular
oped BKV-associated ureteral stenosis. It can also be associated material produced by the bacteria on the surface of the catheter,
with interstitial nephritis or other nephropathies post kidney forming crystalline biofilms. These structures in turn disrupt
transplant. In HSCT recipients, it has been implicated in 10e25% urine drainage, which can lead to infection extension. In
cases of haemorrhagic cystitis.2 Although viruria can be detected contrast, E. faecalis utilizes fibrinogen, released due to bladder
in equal rates in allogeneic and autologous HSCT recipients, it inflammation and deposited on the catheter; both as a nutrient
usually only causes disease in allogeneic recipients with con- source and as an extracellular scaffold by endocarditis and
current graft-versus-host disease. It presents with haematuria, biofilm-associated (Ebp) pili binding.15
dysuria and other lower urinary tract symptoms. The bleeding
and associated clot formation can be sufficient to cause The prostate and prostatitis
obstruction and renal failure.
In haemorrhagic cystitis in children, boys are affected two to The prostate is a genital organ. However, due to its position
three times more commonly than girls; and the proportion due to entwining the neck of the bladder and its function, prostatic in-
Adenovirus can vary geographically e being reported to be fections can be intimately connected to those of the male (genito-
associated with up to 70% in Japan whereas only a fifth of cases )urinary tract.2 Prostatic antibacterial factor, which contains
are linked to acute adenoviral infection in the United States. In zinc, is the most important antimicrobial prostatic secretion.
the post HSC transplant setting, the urinary tract may be involved Patients with chronic bacterial prostatitis have lower levels of
alone or as part of a more widely disseminated infection.2 Other zinc in their prostatic secretions. Bacterial infections of the
viruses that have been less commonly associated with haemor- prostate, both those of ‘acute’ and ‘chronic’ presentations, can
rhagic cystitis post HSCT include the other main human poly- give rise to an associated bacteriuria. Such infections are usually
omavirus pathogen, JC virus, and members of the Herpesviridae caused by Gram-negative uropathogens, including E coli and P.
family, such as herpes simplex virus (HSV), cytomegalovirus aeruginosa.2 Chronic bacterial prostatitis is an important source
(CMV), and human herpesvirus 6 (HHV-6).2 of bacterial persistence in the male urinary tract, and can present
Mycobacterium tuberculosis: the kidneys may be involved in with recurrent bacterial UTIs due to the ‘same’ organism. Most
haematogenous spread of M. tuberculosis organisms from a site antibiotics do not penetrate well into the prostate parenchyma,
elsewhere, usually located in the lung.2 This may occur at the and their efficacy may be hindered by prostatic fluid pH changes
time of initial organism acquisition prior to cellular immunity associated with the infection. The organism strains involved,
developing. The renal cortices are a favoured site for this or- notably E coli, often share similar urovirulence profiles to those
ganism due to the high oxygen tension present. As the host’s associated with pyelonephritis in women.2 Successful eradication
immune system responds, the organisms become entombed in of such foci requires a prolonged course (4e6weeks) of an
calcified foci, though still remaining viable for decades. If the antibiotic that penetrates the prostate reasonably well, such as a
immune response then weakens, the organisms may reactivate fluoroquinolone, infecting organism susceptibility permitting.

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Please cite this article in press as: Walsh C, Collyns T, The pathophysiology of urinary tract infections, Surgery (2017), http://dx.doi.org/10.1016/
j.mpsur.2017.03.007
 BASIC SCIENCE

Conclusion 6 Vivaldi E, et al. Ascending infection as a mechanism in patho-

genesis of experimental non-obstructive pyelonephritis. Exp Biol
UTI is a term used to cover a broad range of clinical pre-
Med 1959; 102: 242e4.
sentations. It is important to further classify the patient’s diag-
7 Brumfitt W, Gargan RA, Hamilton-Miller. Periurethral enterobac-
nosis in terms of upper versus lower and complicated versus
terial carriage preceding urinary infection. Lancet 1987; 1: 824e6.
uncomplicated UTI as this will alter management. Bacteriuria in
8 De Navasquez. Experimental pyelonephritis in the rabbit
itself does not always warrant treatment unless the patient is
produced by staphylococcal infection. J Pathol Bacteriol 1950; 62:
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SURGERY --:- 6 Ó 2017 Published by Elsevier Ltd.

Please cite this article in press as: Walsh C, Collyns T, The pathophysiology of urinary tract infections, Surgery (2017), http://dx.doi.org/10.1016/
j.mpsur.2017.03.007