• Pathogenesis: Primarily ascending from the bladder, only rarely hematogenous
• Etiology: Generally gut flora, gram negative rods. E. coli (#1), proteus, klebsiella,Staph saprophyticus , enterococcus
• Antibacterial host defenses – urine pH, osm, urine flow, mucopolysaccaride has bactericidal properties, inhibitors of adherence, Tamm-Horsfall protein
• Inflammatory response: PMNs, cytokines, immune system, humoral, cell mediated
• Virulence factors of bacteria: (provides survival advantage not Ab resistance) - fimbriae (P, type 1 fimbriae): adhesion protein that aids invasion, prevents destruction, helps colonization and is associated with urosepsis.
• Importantly, virulence is not related to bacterial resistance to antibiotics
• Escherichia coli: Group O serotype highly prevalent in UTIs – likely virulence factor.
• Adhesins: = lectins, which facilitate epithelial binding. Ex: PAP adhesin on P fimbriae; People without inhibitors get UTIs
• Type I fimbriae in E. coli promote persistence of infection and increase the inflammatory response
• Flagella (for motility) is a virulence factor for E. coli; Hemolysin induces formation of pores in the cell membranes
• Siderophore is a protein that is needed for iron acquisition in the iron poor bladder environment
• Proteus mirabilis has many of the same factors as E. coli
• Urease: cytoplasmic enzyme hydrolyzes ureaÞ NH₃ and CO₂ Þ ß urine pHÞ alkaline struvite calculi (stones)Þ safe haven
• Staphylococcus saprophyticus:Þ UTI in young sexually active women. Strong uroepithelium adhesion µ lactosamine residue
• Predisposing factors for development of UTI – Bacterial and host genetics, Women, impaired flow-obstruction, calculi, cysts, neurogenic bladder (DM), prostate enlargement, catheters, stents, procedures, elderly, structural abnormalities/obstruction
• Complicated UTI: diabetes, pregnancy, underlying renal disease, transplant recipients, immunosuppressed patients

Acute pyelonephritis – vs. "Chronic pyelonephritis"

• Intrarenal: this patient presents acutely and you figure out what is the matter.
• hematogenous from another focus (i.e. IV drug users); staph aureus is most common cause
• Clinically – fever, chills, back pain, but no urinary symptoms
• Diagnosis – U/S or CT +/- aspiration Treatment: antibiotics, drainage/ surgery if fail conservative therapy
• perinephric abscess: this is the patient with chronic weight loss whose problem you can’t figure out.
• characterized by collection of pus in the space between the kidney and Gerota's fascia
• caused by rupture of intrarenal abscess into the extrarenal space, or hematogenous/lymphatic seeding
• staph. aureus, E. coli, Proteus mirabilis
• Clinical: may have fever and flank pain, but often present with nonspecific symptoms-weight loss, malaise, nausea
• Diagnosis by imaging study (CT/US). surgical disease

• pathophysiology – silent hematogenous seeding followed by reactivation; cortical caseating granulomas with IN
• can progress to involve destruction medullary collecting system, papillary necrosis Þ usually calcification.
• Calyceal and ureteral involvement can result in stricture formation
• Clinical: insidious, urinary symptoms are common, systemic symptoms are not, may mimic other bacterial infections
• can be complicated by nephrolithiasis and bacterial superinfection
• Diagnosis: "sterile" pyuria is an important clue, isolation of M TB in urine culture (multiple first morning urine samples), newer methods available (ELISA), radiologic evaluation can be helpful: IVU, U/S, CT
• Therapy: long term