What is the pathophysiology of urinary tract infection?

Pathophysiology of Urinary Tract Infection

Urinary tract infections result from uropathogenic bacteria—predominantly E. coli—ascending from the intestinal flora through the urethra into the bladder, where bacterial adhesion to urothelial cells initiates colonization, invasion, and immune-mediated tissue damage.

Bacterial Origin and Ascension

• Uropathogens originate predominantly in the intestinal tract and initially colonize the periurethral region before ascending into the bladder 1
• The ascending route through the urethra is the primary mechanism by which bacteria reach the bladder and potentially the upper urinary tract 2
• Approximately 80% of all UTIs are caused by uropathogenic E. coli (UPEC), making it the dominant pathogen 3, 4

Critical Role of Bacterial Adhesion

Bacterial adherence to the uroepithelium is the essential first step in UTI pathogenesis, allowing bacteria to resist urinary washout and establish infection 1

• UPEC strains express specialized adhesins—particularly P fimbriae and type 1 fimbriae—that bind to specific glycan (sugar) receptors on urothelial cell surfaces 5, 4
• P-fimbriae specifically bind to mannose-containing glycoproteins on the bladder epithelium, initiating the infection cascade 2
• The bacterial protein FimH mediates mannose-dependent binding to host glycoproteins, which is fundamental to UPEC colonization 4
• Patients with increased receptor density on uroepithelial cells or defective natural anti-adherence mechanisms show increased susceptibility to UTI 1

Bacterial Invasion and Intracellular Persistence

• Following adhesion, UPEC invades urothelial epithelial cells where they replicate to form compact aggregates of intracellular bacteria with biofilm-like properties 3
• These intracellular bacterial communities can persist within epithelial cells as quiescent intracellular reservoirs (QIRs), facilitating both establishment and persistence of infection 3
• Host cell invasion allows UPEC to evade extracellular immune defenses and establish long-lasting infections 3
• UPEC-secreted polysaccharides block immune mechanisms to favor intracellular replication 4

Virulence Factors Driving Pathogenesis

Uropathogenic strains express multiple coordinated virulence factors that overcome host defenses and determine infection severity 5

Adhesins

• P fimbriae, mannose-resistant adhesins, and type 1 fimbriae enable bacterial attachment and are more common in pyelonephritis-causing strains 5

Iron Acquisition

• The aerobactin system allows bacteria to scavenge iron in the iron-poor urinary environment, supporting bacterial growth 5, 2

Toxins and Immune Evasion

• Hemolysin production damages host cells and facilitates tissue invasion 5, 2
• K capsule provides resistance to phagocytosis and serum killing 5
• These factors collectively determine whether infection remains localized to the bladder or ascends to cause pyelonephritis 5

Progression to Upper Tract Disease

• Depending on host factors and bacterial virulence characteristics, organisms may ascend from the bladder to cause pyelonephritis 1
• Strains causing pyelonephritis typically express more virulence factors—particularly P fimbriae, aerobactin, and hemolysin—compared to cystitis-causing strains 5, 2
• Upper tract involvement is characterized by systemic symptoms including fever, flank pain, and costovertebral angle tenderness 6

Immune-Mediated Tissue Damage

Renal scarring and permanent damage occur not from bacterial invasion alone, but from the host immune response when treatment is delayed 2

• Toxic oxygen radicals released during ischemic episodes and prolonged phagocytic respiratory burst cause renal tissue damage 2
• This damage is most pronounced when effective antibacterial treatment is delayed or when diagnosis is not made early 2
• Both T and B lymphocyte responses generate antibodies that assist in bacterial eradication when effective therapy is administered 2
• Chronic pyelonephritis leads to progressive loss of renal tissue and function, potentially progressing to end-stage renal disease 2

Host Defense Mechanisms

• Natural anti-adherence mechanisms exist in humans, including surface glycans on the urothelial surface and secreted glycoproteins that prevent or limit UPEC adhesion 1, 4
• Defects in these protective mechanisms or alterations in receptor density increase UTI susceptibility 1
• The normally efficient host defense mechanisms—including urinary flow, bladder emptying, and mucosal immunity—must be overcome by bacterial virulence factors for infection to establish 1

Virulent Clonal Groups

• Virulence factors are more common among certain genetically related groups of E. coli that constitute virulent clones within the larger bacterial population 5
• In general, the more virulence factors a strain expresses, the more severe an infection it can cause 5
• Specific virulence factor profiles favor different clinical presentations: some promote pyelonephritis, others cystitis, and others asymptomatic bacteriuria 5

Complicated UTI Pathophysiology

• In complicated UTIs associated with diabetes, instrumentation, stones, or immunosuppression, organisms other than E. coli become more prevalent 2
• Structural abnormalities (obstruction, catheters, high post-void residual volumes) provide bacterial niches that resist clearance and promote persistence 6
• Anatomical factors such as cystoceles, diverticula, and fistulae increase infection risk by impairing normal defense mechanisms 6