012-3-11 Definition Urinary Tract a Urinary tract infections are acute Infections(UTIs) chronic inflammatory reactions caused by proliferation of pathogenic microorganisms Tongying Zhu existing in the urinary tract Huashan Hospital Fudan Definition(cont Classification of utis a Infections of the urinary tract can be subdivided into two general anatomic Asymptomatic bacteriuria Symptoms O Lower tract infection(urethritis and cystitis radic(sI UT1/6 mo and s2 UTIs/yr) a Upper tract infection(pyelonephritis, intrarenal Recurrent(22 UTIs/ 6 mo or 23 UTls/yr) and perinephric abscesses) Reinfection Complicating factors Complicated(see text UTl=urinary tract infection. Epidemiology Epidemiology(cont s Worldwide, at least 150 million cases of symptomatic UTIs who have utis is lower nales, who are also more likely to hav number of cases ymptomatic bacteriuria. a 90% of patients have cystitis and 10% have pyelonephritis (short urethra, also be the result of sexual abuse n Sporadic in about 70% of patients and recurrent in 25%. m In young man under 50, UTIs are rare and are often the result n About 2% have complicated infections related to factors that of underlying infections of the prostate. tic and asymptomatic UTIs erity are included, the Women often the result of atrophic vagin equency of complicated infections is about 8%. ence of prostate hyperplasia or cancer
2012-3-11 1 Urinary Tract Infections(UTIs) Tongying Zhu Huashan Hospital Fudan University Definition Urinary tract infections are acute or chronic inflammatory reactions caused by proliferation of pathogenic microorganisms existing in the urinary tract. Definition(cont.) Infections of the urinary tract can be subdivided into two general anatomic categories: Lower tract infection (urethritis and cystitis) Upper tract infection (pyelonephritis, intrarenal and perinephric abscesses) Classification : Table 292-1 Classification of UTIs Epidemiology Worldwide, at least 150 million cases of symptomatic UTIs occur each year. The number of patients who have UTIs is lower than the number of cases. 90% of patients have cystitis and 10% have pyelonephritis 90% of patients have cystitis and 10% have pyelonephritis. Sporadic in about 70% of patients and recurrent in 25%. About 2% have complicated infections related to factors that increase the risk of establishment and management of bacteriuria. If factors that can increase the severity are included, the frequency of complicated infections is about 8%. Epidemiology (cont.) In very young child, UTIs more common in boy. Later in childhood and adult, symptomatic UTIs are more common in females, who are also more likely to have asymptomatic bacteriuria. (short urethra also be the result of sexual abuse) (short urethra, also be the result of sexual abuse) In young man under 50, UTIs are rare and are often the result of underlying infections of the prostate. In elderly people, both symptomatic and asymptomatic UTIs are common. Women: often the result of atrophic vaginal mucosa Men: often the consequence of prostate hyperplasia or cancer
012-3-11 Microbial Etiology of UTIs Epidemiology(cont NICAL CHARACTERISTICs a UTls is also the most common type of hospital-acquired infection because of the frequent use of bladder-catheters (catheter-associated infection) Most comcon daring sanmar Urethral syndrome Pathogenesis s In the vast majority of UTIs, bacteria gain access to the n About 1/3 n with dysuria and frequency have either an adder via the urethra m Ascent of bacteria from the bladder may follow and is mpletely sterile cultures -previously defined as having probably the pathway for most pyelonephritis urethral syndrome. a y no pyuria(and little objective evidence of infection) s In rare cases, bacteriuria and funguria may result from D Low counts(102 to 10ml)of typical bactenal uropathogens n These bacteria are probably the causative agents and associated with genous pyelonephritis occurs most often in ed patients who are either chronically ill or D Can be isolated from a suprapubic aspirate receiving immuno-suppresive therapy rimary focus of the infection is usually an infection at a site outside the renal tract, such as endocarditis Pathogenesis(cont Pathogenesis(cont s The vaginal introitus and distal urethra are normally colonized by diphtheroids, streptococcal and a In the normal male urethra. the distance between the staphylococcal species, lactobacilli, but not by the enteric G(-)bacilli end of the urethra and the bladder is too long to allow ding transport of bacteria to the bladder The factors that predispose to periurethral colonization with G()bacilli remain poorly understood. de when there is a turbulent urine flow a Alteration of the normal vaginal flora by antibiotics, other with a stricture or obstruction of the urethra. as a prostate hyperplasia, and when the patient has a appear to play an important role. n Loss of the normally dominant H2O2-producing ctobacilli in the vaginal flora appears to facilitate colonization by Ecoli
2012-3-11 2 Epidemiology (cont.) UTIs is also the most common type of hospital-acquired infection because of the frequent use of bladder-catheters. (catheter- associated infection) Microbial Etiology of UTIs Urethral syndrome About 1/3 of women with dysuria and frequency have either an insignificant number of bacteria in midstream urine cultures or completely sterile cultures ---previously defined as having urethral syndrome. ¼ no pyuria (and little objective evidence of infection) ¾ pyuria Low counts(102 to 104/ml) of typical bacterial uropathogens These bacteria are probably the causative agents and associated with pyuria Can be isolated from a suprapubic aspirate Respond to appropriate antimicrobial therapy Pathogenesis In the vast majority of UTIs, bacteria gain access to the bladder via the urethra. Ascent of bacteria from the bladder may follow and is probably the pathway for most pyelonephritis. In rare cases, bacteriuria and funguria may result from In rare cases, bacteriuria and funguria may result from the hematogenous dissemination of bacteria to the kidneys. Hematogenous pyelonephritis occurs most often in debilitated patients who are either chronically ill or receiving immuno-suppresive therapy. Primary focus of the infection is usually an infection at a site outside the renal tract, such as endocarditis. Pathogenesis(cont.) The vaginal introitus and distal urethra are normally colonized by diphtheroids, streptococcal and staphylococcal species, lactobacilli, but not by the enteric G(-) bacilli. The factors that predispose to periurethral colonization with G(-) bacilli remain poorly understood. Alteration of the normal vaginal flora by antibiotics, other genital infections, or contraceptives (esp. spermicide) appear to play an important role. Loss of the normally dominant H2O2-producing lactobacilli in the vaginal flora appears to facilitate colonization by E.coli. Pathogenesis(cont.) In the normal male urethra, the distance between the end of the urethra and the bladder is too long to allow ascending transport of bacteria to the bladder. Transport is possible when there is a turbulent urine flow (such as with a stricture or obstruction of the urethra, as a result of prostate hyperplasia, and when the patient has a bladder catheter )
012-3-11 Pathogenesis(cont) Pathogenesis(cont) u When bacteria have reached the bl a The female urethra is short and allows transport of ia is facilitated by incom bacteria to the bladder in healthy individuals With many uropathogens, such tra is facilitated by bladder through the ureter to the renal pelvis and the renal adherence of the bacteria to urethral epithelial cells parenchyma. n Sexual intercourse results in increased numbers of a This transport may be facilitated b cteria in the periurethral area of the vagina and the mic defects of the ureters or the kidneys distal part of the urethra, increasing the risk of vesicoureteral reflux o adhesion to the ureter mucosa Pathogenesis(cont Bacterial virulence factors a Uropathogenic E Coli: a Whether bladder infection occurs depends a belongs to a small no of specific o, K and H serogroups on interacting effects of the pathogenicity n Easy to adherence to uroepithelial cells(fimbriae) D After attachment, initiates some important events in epithelial of the strain the inoculum size. and the local and systemic host defense mechanism a These properties are not needed for infection of the Bladder catheterization and utis Host factors complicating bacteriuria FACTORS s Bladder catheterization leads to bacteriuria or funguria in almost all patients who have had their catheters for more the growth of microorganisn a Urosepsis, resulting from diss acteria from the urine to the blood may ha or changing the catheter. infections involving the kidneys a The urethral mucosa may also be damaged by crystals Chronic pyelonephritis that form on the catheter surface
2012-3-11 3 Pathogenesis(cont.) The female urethra is short and allows transport of bacteria to the bladder in healthy individuals. With many uropathogens such tr With many uropathogens, such transport ansport is facilitated by is facilitated by adherence of the bacteria to urethral epithelial cells. Sexual intercourse results in increased numbers of bacteria in the periurethral area of the vagina and the distal part of the urethra, increasing the risk of bacteriuria. Pathogenesis(cont.) When bacteria have reached the bladder, the establishment of bacteriuria is facilitated by incomplete bladder emptying Pyelonephritis results from ascending bacteriuria from the bladder through the ureter to the renal pelvis and the renal bladder through the ureter to the renal pelvis and the renal parenchyma. This transport may be facilitated by: host factors such as anatomic defects of the ureters or the kidneys, vesicoureteral reflux adhesion to the ureter mucosa Pathogenesis(cont.) Whether bladder infection occurs depends on interacting effects of the pathogenicity of the strain, the inoculum size, and the local and systemic host defense mechanism. Bacterial Virulence Factors Uropathogenic E. Coli: belongs to a small no. of specific O, K and H serogroups. Easy to adherence to uroepithelial cells (fimbriae) After attachment initiates some i After attachment, initiates some important mportant events in epithelial events in epithelial cells(secretion IL6, IL8, induction of apoptosis and epithelial cell desquamation) Secretion hemolysin and aerobactin and are resistant to the bactericidal action of human serum These properties are not needed for infection of the compromised urinary tract Host factors complicating bacteriuria Bladder catheterization and UTIs Bladder catheterization leads to bacteriuria or funguria in almost all patients who have had their catheters for more than 1 week. Formation of a biofilm on the catheter surfaces facilitates the gro th of microorganisms the growth of microorganisms. Urosepsis, resulting from disssemination of bacteria from the urine to the blood may happen during the removing or changing the catheter. The urethral mucosa may also be damaged by crystals that form on the catheter surface
012-3-11 Pregnancy and UTIs Pregnancy and UTls(cont a UTIs are detected in 2-8%of pregnant women. ition to upper tract infection during s Asymptomatic bacteriuria frequently harbor organisms that ess virulent than those causing symptomatic infections. n Temporary incompetence of the vesicoureteral valv m Fully 20-30% of pregnant women with asymptomatic a Bladder catheterization during or after delivery bacteriuria subsequntly develop pyelonephritis. a Risk of UTIs during pregnancy a Increased incidences of low-birth-weight infants 口 Premature delivery Genetic Factors and UTIs P blood group a Host genetic factors influence susceptibility to UTIs m P blood group system, classification of human blood based on the presence of any of three substances experienced recurrent Utis than among controls. known as the P. P, and Pk ans on the surfaces of s The number and type of receptors which bacteria may attach are at opart geneticaly a There are five phenotypes in the P blood group system: P, P2, P, P2, P a P2 phenotype -consists of the P and P< antigens a Many of these structures are components of blood group antigens and are present on both erythrocytes and o P, phenotype---Pk antigen o Extremely uroepithelial cel a p phenotype-no antigens unc ommon P blood group antigens assigned roles in the P blood group antigens assigned roles in the pathophysiology of UTIs pathophysiology of UTIs(cont) a The P blood group antigens are glycan structures, expressed not only on red cells, but also on other tissues, including the enotype has a higher risk, relative to P2 phenotype is of utis by the observation that various uropathogenic observation that adhesion of strains of Escherichia coli express adhesins that bind to the elonephritic strain of E. coli to renal tissue is mediated Gala1-4Gal moiety of the Pk and P, antigens acterial adhesin specific for the Gala 1-4Gal structure and that deficiency of the adhesin severely s The P, detern attenuates the pyelonephritic phenotype of the organism. attachment of bacteria to the lining of the urinary tracing individuals and may facilitate bacterial infection by media
2012-3-11 4 Pregnancy and UTIs UTIs are detected in 2-8% of pregnant women. Asymptomatic bacteriuria frequently harbor organisms that less virulent than those causing symptomatic infections. Fully 20-30% of pregnant women with asymptomatic bacteriuria subsequntly develop pyelonephritis. Pregnancy and UTIs(cont.) The predisposition to upper tract infection during pregnancy results from: Decreased ureteral tone Decreased ureteral peristalsis Decreased ureteral peristalsis Temporary incompetence of the vesicoureteral valve Bladder catheterization during or after delivery Risk of UTIs during pregnancy Increased incidences of low-birth-weight infants Premature delivery Newborn mortality Genetic Factors and UTIs Host genetic factors influence susceptibility to UTIs. A maternal history of UTI is more often found among women who have experienced recurrent UTIs than among controls. The number and type of receptors on uroepithelial cells to which bacteria may attach are at least in part genetically determined. Many of these structures are components of blood group antigens and are present on both erythrocytes and uroepithelial cells P blood group P blood group system, classification of human blood based on the presence of any of three substances known as the P, P1, and Pk antigens on the surfaces of red blood cells. There are five phenotypes in the P blood group system: P1, P2, P1 k, P2 k, P P1 phenotype --- displays all three P antigens P2 phenotype --- consists of the P and Pk antigens P1 k phenotype -- P1 and Pk antigens P2 k phenotype --- Pk antigen only p phenotype --- no antigens Extremely uncommon P blood group antigens assigned roles in the pathophysiology of UTIs The P blood group antigens are glycan structures , expressed not only on red cells, but also on other tissues, including the urothelium . A role for P blood group antigens in the pathogenesis of UTIs is implied by the observation that various uropathogenic strains of Escherichia coli express adhesins that bind to the Galα1–4Gal moiety of the Pk and P1 antigens. The P1 determinant is expressed on the urothelium of P1 individuals and may facilitate bacterial infection by mediating attachment of bacteria to the lining of the urinary tract P blood group antigens assigned roles in the pathophysiology of UTIs (cont.) This hypothesis is supported by the observation that P1 phenotype has a higher risk, relative to P2 phenotype, for UTIs and pyelonephritis. It is also supported by the observation that adhesion of a pyelonephritic strain of E. coli to renal tissue is mediated by a bacterial adhesin specific for the Galα1–4Gal structure and that deficiency of the adhesin severely attenuates the pyelonephritic phenotype of the organism
012-3-11 Clinical manifestations Cystitis s The onset of cystitis is rapid, and symptoms develop a Cystitis over less than 24 hours s Patients with cystitis usually report dysuria, frequency, a Pyelonephritis urgency, and suprapubic pain a Urine is bloody in -30% of cases. a Urosepsis s Clinically, it is often impossible to differentiate between cystitis and urethritis caused by chlamydia, ureaplasma Cystitis(cont. Py a Fever is unusual among patients with cystitis a rapid onset, with or without a The patients are often with the fever and flank pain Cystitis patients normally have symptoms for 3 to 5 days m About 1/3 of patients develop bacteremia Antibiotic therapy does not markedly reduce the duration a The typical flank pain results from inflammation and edema of the renal parenchyma. Differential diagnosis of pyelonephritis Urosepsis is renal calculi. which may result in a similar location of the pain but ning condition caused by characteristically do not cause fever. ition of bacteria from the urine in a patient with with flank pain similar to that in a patient with right-sided pyelonephritis (and most. eason for urosepsis is withdrawal nsertion)of a bladder catheter (urinanalysis can make differential diagnosis) a Therefore, uroseptic patients do not always have a renal infection
2012-3-11 5 Clinical manifestations Cystitis Pyelonephritis Urosepsis Cystitis The onset of cystitis is rapid, and symptoms develop over less than 24 hours. Patients with cystitis usually report dysuria, frequency, urgency and suprapubic pain urgency, and suprapubic pain. Urine is bloody in ～30% of cases. Clinically, it is often impossible to differentiate between cystitis and urethritis caused by chlamydia, ureaplasma, or gonococci. Cystitis (cont.) Fever is unusual among patients with cystitis. In sexually active women, cystitis commonly occurs 24 to 48 hours after intercourse esp without post 48 hours after intercourse, esp. without post-voiding voiding . Cystitis patients normally have symptoms for 3 to 5 days. Antibiotic therapy does not markedly reduce the duration. Pyelonephritis Pyelonephritis also has a rapid onset, with or without preceding cystitis symptoms. The patients are often with the The patients are often with the fever and flank pain flank pain. About 1/3 of patients develop bacteremia. The typical flank pain results from inflammation and edema of the renal parenchyma. Differential diagnosis of pyelonephritis An important differential diagnosis is renal calculi, which may result in a similar location of the pain but characteristically do not cause fever. Patients with appendicitis and cholecystitis can present with flank pain similar to that in a patient with right-sided pyelonephritis. (urinanalysis can make differential diagnosis) Urosepsis Urosepsis is a life-threatening condition caused by dissemination of bacteria from the urine in a patient with bacteriuria. The most common reason for urosepsis is withdrawal (and sometimes insertion) of a bladder catheter. Therefore, uroseptic patients do not always have a renal infection