UTIs
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| uncomplicated urethritis or cystitis | painful urination
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| some cases of pyelonephritis | fever, sepsis, decreased kidney function
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| Etiologic agents of urinary tract infections | 90% caused by E. coli; others include: enterobacteriaceae family, pseudomonads, enterococci, yeast (candida)
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| Increased risk or UTI in sexually active women a/w: | use of diaphragm with spermicide d/t inc colonization of vagina w/uropathogens; Spermicide inc adherence of E. coli to vaginal epithelial cells
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| Cystitis | infxn of bladder wall; freq/urgent urination & dysuria (pain); Tender suprapubic area; Bacteria & WBCs common in urine (50% have blood); malodorous
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| Pyelonephritis | infxn of kidney & renal pelvis; mc follows bladder infxn; Acute can lead to chronic
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| Acute pyelonephritis | presence of WBCs, cellular casts, bacteria and protein in urine
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| Chronic pyelonephritis | gradual nephron loss and renal failure
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| Urethritis | inflam of urethra usu caused by bacteria
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| Glomeruloneprhitis | inflam of glomeruli in nephrons; glomerular capillary network becomes leaky allowing plasma ptn & RBCs to be excreted in urine
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| Bugs a/w Cystitis | **E. coli**, Klebsiella, Proteus, Staphylococcus saprophyticus, Serratia marcescens, Pseudomonas aeruginosa, Enterococcus faecalis; mc in women d/t proximity of short urethra to fecal contamination
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| Prostatitis | inflam of prostate gland; acute infxn is often an extension of a bladder or uretha; follows catheterization
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| Virulence Factors a/w UTIs | adherence to vaginal wall and uroepithelial cells; Cytotoxic necrotizing factors; Hemolysin; Genes are linked together as multigene segments called "Pathogenicity Islands" that are abscent in normal fecal coliforms
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| Pathogenicity Islands | mobile genetic elements (in addition to virulence plasmids) that encode secreted virulence protein components of: Fimbriae, Pili, Outer membrane ptns; all surface components mediating colonization, attachment & location of infxn
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| Adhesive capacities | E. coli pyelonephritis isolates adhere better than E. coli cystitis isolates; urinary isolates adhere to uroepithelial cells more strongly than fecal isolates
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| Escherichia coli | G(-) rods; facultative anaerobes; mc source of urinary tract infxn d/t fecal contamination of genital area; Adheres to mucosa w/pili causing tissue damage; Endotoxin (LPS) causes inflam; Treat w/PCN or Ciprofloxacin
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| Col V plasmid - codes for Siderophores | captures Fe and brings it in for E. coli to grow
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| Hemolysin | damages host cells; releases Fe from RBCs
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| Enterochelin | chelates Fe for bacterial uptake
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| K1 antigen | impedes phagocytosis, blocks binding of C3b opsonin
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| P-pili | allows bacterial to bind to P blood group antigens on urinary tract cells (esp in kidneys)
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| Type 1 Pili | allows bacteria to bind to bladder epithelium, Tamm-Horsfall glycoprotein & D-mannose residues on variety of cells
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| Proteus sp (vulgaris, mirabilis, etc) | G(-) rods, facultative anaerobes; Opportunistic (catheters); Enteric bacteria (same as E. coli, salmonella, shigella, enterobacter, serratia); *Urease Positive --> converts urea to ammonia raising pH*; highly motile; swarms agar
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| Proteus mirabilis | 2nd to E. coli in causing UTIs; commonly infects kidneys (>E.coli); Non-traditional infxs occuring in individuals w/abnormalities in UT & elderly w/long-term catheters
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| Proteus mirabilis pathogenicity | invades & attaches to host epithelial cells; resists host defenses by producing: Pore-forming hemolysins, Endotoxin (bc G-), Urease, Adhesins, Polysaccharide capsule, Pili, fimbrae, flagella, Biofilms
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| Proteus mirabilis: Urease activity | hydrolyzes urea; produces ammonia and CO2; raises pH; precipitates nml soluble ions to form stones (calculi) --> Mg-ammonium-phosphate (struvite) & Calcium-phosphate (apatite)
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| Proteus mirabilis: Swarming ability | critical to the virulence of the sp.; expression of virulence determinants (protease, hemolysin) specific to swarmer bacteria
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| Proteus mirabilis: treatment | PNPG (anti-swarm agent inhibits hemolysins, proteases, flagella; may prevent invasion of urothelial cells); Broad spectrum PCNs & Cephalosporins (not nitrofurantoin or tetracycline); Inc resistance to: Ampicillin, Ciprofloxin, Trimethoprim
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| Staphylococcus saprophyticus | G+ cocci; Nitrite neg, non(gamma)-hemolytic; Catalase +, Coagulase neg; Resistant to Novobiocin; UTI common in sexually active women (5-15% of UTIs) "honeymoon cystitis"
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| Serratia marcescens | G(-) bacilli; facultative anaerobes; Enterobacteriaceae family; Positive for (DNAse, Gelatinase, Lipase, Citrate utilization); Opportunistic pneumonia & UTI agent (used in army experiment)
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| Enterococcus faecalis | aka: (Grp D streptococci, Streptococcus faecalis); GI tract normal flora, causative agent for: (endocarditis, cystitis, wound infections); Blood agar (gamma/some alpha-hemolysis); Bile-esculin agar (black color); also gros on 6.5% NaCl; *Catalase negative
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| Interesting facts about Enterococcus faecalis | 25% of genome is exogenously acquired DNA (lateral gene transfer btw genus & species; Virulece factors from Staph and Strep); leading cause of nosocomial infxns; Pathogenicity island codes for toxins that form holes in cell wall & allow adherence
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| Enterococcus faecalis: Virulence and Treatment | development of Abx resistance (d/t ability to acquire mobile gene elements); Tx (amoxicillin, ampicillin, vancomycin-some resistant strains exist)
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| Klebsiella sp | G(-), non-motile, rod, aerobic, endotoxin & enterotoxin activity; Ubiquitous (may colonize skin, pharynx, GI tract); Large mucoid colonies w/large mucoid polysaccharide capsule "K antigen" that protects against phagocytosis & aids in adherence
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| Klebsiella pneumoniae, Klebsiella oxytoca | opportunistic pathogens; found in environment/mucosal surfaces; passed by hands in hospital; Common infxns: UTI, lower resp tract (red current jelly sputum/hemoptysis), biliary tract, surgical wounds
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| Klebsiella sp Clinical Syndromes & Treatmtent | UTIs; Primary pneumonia; wound infxns, bacteremia, meningitis, diarrhea by enterotoxigenic strains; Cephalosporins
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| Candida sp. | normal urogenital tract flora in 20-50% of healthy women; Inc risk of infection with: (broad-spectrum Abx, pregnancy, diabetes, AIDS, surgery, in-dwelling catheters); Treat topically with Nystatin or Clotrimazole
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| Candida Germ Tube Formation | triggered by environmental cues (pH, temp, chemicals); adherence/virulence factor; induced by serum at 37*C; 1st step in transition from yeast to hyphae; D-glucose (active component in serum for induction; can be inhibited by glucose oxidase at pH 7-8)
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| Catheter-associated UTIs (CAUTI) | UT is mc site of nosocomial infxns (40%); 66-86% of nosocomial UTIs follow catheterization (duration inc incidence)
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| Pathogens a/w CAUTIs | **Pseudomonas cepacia, Serratia marcescens (neither are normal flora)**; E. coli, Klebsiella, Proteus, Enterococcus, Enterobacter, Candida; biofilms assist in stickiness to plastic
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| Extraluminal CAUTI | early (occurs at insertion site); Late (occurs by capillary action)
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| Intraluminal CAUTI | Intraluminal (break in closed drainage; contamination of collection bag urine)
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| Catheter colonization by Proteus mirabilis | leads to precipitation of phosphatic salts, stone formation and blockage
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| Schistosoma haemotobium: Urinary Tract schistosomiasis | can lead to renal failure d/t obstructive uropathy, pyeloneprhitis, bladder carcinoma
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| Schistosoma haemotobium: Female genital schistosomiasis | causes lesions in lower female genital tract; may facilitate spread of STDs such as HIV and HPV
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| Urinary Schistosomiasis: Clinical manifestations and Lab studies | dysuria, urinary frequency, terminal hematuria; ID and speciate eggs in urine; urinary excretion of eggs is not uniform throughout day (more likely btw 10am and 2pm; quantify with 24hr collection)
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| Urinary Schistosomiasis: Diagnostics | UA (culture for associated infections); UTI caused by Salmonella is suspicion for this infection (esp if blood cultures show Salmonella); Blood chemistries (renal panel); CBC (check for anemia and eosinophilia)
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| Urinary Schistosomiasis: Treatment | Antihelmintics (Praziquantil damages tegument membrane, exposing worm to immune defenses); Test effectiveness of treatment with "egg viability test
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| Routine Urinalysis: Chemical Testing - Nitrite | detects bacteriuria (some convert nitrate to nitrite; usu G(-)s); dipstic method forms diazonium salt forming a pink azodye; False positives if contaminated or if stored improperly
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| Routine Urinalysis: Chemical Testing - Leukocytes | dipstick detects leukocyte esterase activity in WBCs (granulocytic cells); detects lysed and intact; indixylcarbonic acid ester reacts w/diazonium salt to form purple azodye
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| Routine Urinalysis: Chemical Testing - Hemoglobin (blood) | in renal dx or trauma, RBCs enter urine & become hemolyzed; Hemolytic anemia (Hb is filtered into urine from transfusion rxns, severe burns, infxns, strenuous exercise); Dipstick orthotoluidine reacts w/Hb & organic peroxide to turn blue
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| UTI: Treatment | most treated with: Trimethoprim-sulfamethoxazole (amoxicillin) or Fluoroquinolones (Levaquin); Those caused by Chlamydia trachomatis or Mycoplasma hominis may require *tetracycline or doxycycline*
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| Recurrent UTIs | 20% of women suffer >1; bacterial strains will differ; Related to "nonsecretors" for certain blood group antigens (cells lining urethra/vagina are more susceptible to bacterial attachment)
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| Recurrent UTIs: Secretors vs Nonsecretors | 80% of population secrete A, B, & H antigens into body fluid w/same specificity as Ag on RBC membrane; trait is a/w Se gene which is inherited independently from other blood Ags; H-gene is precursor for ABO (all secretors secrete H gene)
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| ABO Blood Group System Biochemistry | Oligosaccharide chain precursor: H-gene produces enzyme that puts on L-fucose; A-gene produced enzyme that puts on A-antigen; B-gene produces enzyme that puts on B-antigen
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| Recurrent UTIs: Secretor Testing | useful in determining blood group types on individuals whose RBC antigens are poorly developed or missing (also determining blood grps in forensic medicine)
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| Recurrent UTIs: Nonsecretors | 20% of population; homozygous for Se gene and do not secrete ABH antigens; All bombay individuals are nonsecretors since they don't produce H, A, or B antigens
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