Urinary tract infections - PATHOPHYSIOLOGY (PHARM D)

UTI, etiology,symptoms, pathophysiology, diagnsosis and treatment, complications

1. URINARY TRACT INFECTIONS Infections of the urinary tract which represents a wide variety of syndromes including urethritis, cystitis, prostatis and pyelonephitis . Classified into: Uncomplicated UTI : Infection in healthy female who lacks structural or functional abnormalities of the urinary tract . Complicated UTI : Complicated infections associated with predisposing lesions of the urinary tract.

2. ETIOLOGY The bacteria causing UTIs usually originate from bowel flora of the host . The most common cause of uncomplicated UTIs is Escherichia coli , which accounts for 85% of community-acquired infections. Additional causative organisms in uncomplicated infections include Staphylococcus saprophyticus (5% to 15%), Klebsiella pneumoniae, Proteus spp., Pseudomonas aeruginosa , and Enterococcus spp . (5% to 10%).

3. PATHOPHYSIOLOGY ROUTE OF INFECTION In general, organisms gain entry into the urinary tract via three possible routes: the ascending, hematogenous (descending), and lymphatic pathways . The female urethra usually is colonized by bacteria believed to originate from the fecal flora. The short length of the female urethra and its proximity to the perirectal area make colonization of the urethra likely . Bacteria have reached the bladder, the organisms quickly multiply and can ascend the ureters to the kidneys . Infection of the kidney by hematogenous spread of microorganisms usually occurs as the result of dissemination of organisms from a distant primary infection in the body . There are lymphatic communications between the bowel and kidney, as well as between the bladder and kidney.

4. HOST DEFENSE MECHANISMS The normal urinary tract generally is resistant to invasion by bacteria and is efficient in rapidly eliminating microorganisms that reach the bladder. The urine under normal circumstances is capable of inhibiting and killing microorganisms. The factors thought to be responsible include a low pH , extremes in osmolality , high urea concentration, and high organic acid concentration . Bacterial growth is further inhibited in males by the addition of prostatic secretions . The epithelial cells of the bladder are coated with a urinary mucus or slime called glycosaminoglycan . This thin layer of surface mucopolysaccharide is hydrophilic and strongly negatively charged. When bound to the uroepithelium , it attracts water molecules and forms a layer between the bladder and urine.

5. BACTERIAL VIRULENCE FACTORS The mechanism of adhesion of gram-negative bacteria, particularly E. coli, is related to bacterial fimbriae that are rigid hair like appendages of the cell wall. Other virulence factors include the production of hemolysin and aerobactin . Hemolysin is a cytotoxic protein produced by bacteria that lyses a wide range of cells , including erythrocytes, PMNs, and monocytes. E . coli and other gram-negative bacteria require iron for aerobic metabolism and multiplication. Aerobactin facilitates the binding and uptake of iron by E. coli.

6. TREATMENT Urinary analgesics such as phenazopyridine hydrochloride are used frequently by many clinicians . Conventional therapy consisted of an effective oral antibiotic administered for 7 to 14 days . A number of antibiotic regimens have been used as empirical therapy, including an intravenous fluoroquinolone , an aminoglycoside with or without ampicillin , and extended-spectrum cephalosporins with or without an aminoglycoside . Other options include aztreonam , the β- lactamase inhibitor combinations (e.g., ampicillin sulbactam , ticarcillin - clavulanate , and piperacillin-tazobactam ), carbapenems (e.g ., imipenem , meropenem , or ertapenem ), or intravenous trimethoprim-sulfamethoxazole .

7. COMPLICATIONS Complications of a UTI may include: Recurrent infections , especially in women who experience two or more UTIs in a six-month period or four or more within a year. Permanent kidney damage from an acute or chronic kidney infection (pyelonephritis) due to an untreated UTI. Increased risk in pregnant women of delivering low birth weight or premature infants. Urethral narrowing (stricture) in men from recurrent urethritis, previously seen with gonococcal urethritis. Sepsis , a potentially life-threatening complication of an infection, especially if the infection works its way up your urinary tract to your kidneys.