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M2 Renal > 1/30/17 UTI Pathophyiology - Lebowitz > Flashcards

1/30/17 UTI Pathophyiology - Lebowitz Flashcards

1
Q

bacteriuria

pyuria

UTI

A

bacteriuria: presence of bacteria in urine (normally sterile)

pyuria: presence of WBCs in urine → gen indication of infl response of urothelium

UTI: infl response of urothelium to bacterial invasion, usually assoc with bacteriuria and pyuria

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2
Q

clinical dx of cystitis

A

clinical findings will predice UTI to 90% prob

culture not recommended or required in uncomplicated cases

only recommended if:

  • complicated URI
  • atypicaly sx
  • persistent sx post-tx
  • recurrent sx within a month

symptoms/associations:

  • dysuria, frequency, urgency
  • suprapubic pain
  • hematuria
  • fever: inconsistent finding
  • sexual history
  • hx of prior inf
  • antibiotic use
  • sx suggesting upper tract inf
  • acute urethral syndrome
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3
Q

mechanisms of:

  • dysuria
  • freq/urgency
  • hematuria
  • suprapubic tenderness
  • fever/sweats/chills
  • CVA tenderness/flank pain
A
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4
Q

ddx of UTI

A
  • UTI
  • urethritis (chlamydia, gonorrhea, herpes)
  • vaginitis (fungal, trichomonas, bacterial)
  • prostatitis
  • nephrolithiasis
  • interstitial cystitis
  • trauma
  • urinary TB
  • urinary tract neoplasm
  • intraabd abscess
  • sepsis (non-GU source)
  • overactive bladder
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5
Q

basic principles of dx/testing

urine?

contamination?

definitive dx

A

bladder urine should be sterile

BUT voided specimens will have some amount of contamination (surface)

use approp collection/handling methods

definitive diagnosis by means of:

  • urinalysis
  • urine culture
  • quantitative urine culture
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6
Q

pathogenesis of UTI

A
  • contamination
    • orgs introduced during collection of processing urine
  • colonization
    • organisms present in urin, but no illness/no sx
    • variable significance
    • doesn’t necessarily req tx
  • infection (UTI)
    • combo of pathogens within urinary system and infl response
    • symptomatic, requires tx
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7
Q

types of UTI, pathogenesis

uncomplicated

complicated

recurrent

reinfection

persistent

A

uncomplicated: inf in healthy pt with anatomically and functionally normal urinary tract

complicated: inf assoc with factors incr colonization and decr efficacy of tx

  • anatomical/functional abnormality of urinary tract (enlarged prostate, stone disease, diverticulum, neurogenic bladder)
  • immunocompromised host
  • MDR bacteria

recurrent: occurs after documented inf resolved

reinfection: new event w reintro of bacteria into urinary tract

persistent: caused by same bacteria from focus of inf

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8
Q

progression of UTI

(bottom to top)

A
  1. colonization
  2. uropithelium penetration
  • role of FIMBRIA
  • biofilms
  1. ascension
  2. pyelonephritis: infection of renal parenchyma
  3. acute kidney injury
  • tubular obstruction/damage → interstitial edema
  • interstitial nephritis → AKI
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9
Q

success of UTI bacterial inf depends on…

A
  1. size of inoculum
  2. host defense mechs
  3. virulence factors of bacteria
    * bacterial adherence (mediated by surface mols and pili → promote attachment, allow persistence)
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10
Q

host defenses of urinary tract

A

1. urine

  • acidic pH
  • high osmolality
  • inhibitors of bact adherence
  • comp inhibitors of attachment to uroepithelial cells
  • mechanical flushing

2. mucosal immunity

  • urothelial cytokines/chemokines
  • mucopolysacch lining → more difficult to penetrate
  • mucosal IgA
  • sex-specific
    • women: protective vaginal flora
    • men: prostatic secretions w bactericidal Zn; longer urethra
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11
Q

host factors defending against UTI:

periurethral and urethral region

urinary factors

bladder

kidney

A

periurethral/urethral region colonized by

  • Lactobacilli
  • coagulase (-) staph
  • Cornyebacterium
  • Streptococci

*changes in E2, low vaginal pH, cervical IgA affect colonization

urinary factors

bladder

  • epithelium expressed TLRs → recog bacteria, initiate infl response, induce exfoliation of cells/allow excretion of bacterial colonization

kidney

  • local immunoglobulin/ab synth in response to inf → IgG, secretory IgA
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12
Q

alterations in defense mechs that predispose to UTIs

A
  • reduced urine flow
  • factors promoting colonization
    • sexual activity, spermicides (incr binding), estrogen depletion, antibiotic explosure (kill flora)
  • factors that facilitate ascent
    • catheterization
    • urinary/fecal incontinence
    • residual urine w bladder wall ischemia
    • VUR (vesicoureteral reflux)
  • underlying disease (diabetes, papillary necrosis, HIV)
  • pregnancy
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13
Q

features of uropathogenic bacteria

pili

A

pili: surface appendanges used by bateria to adhere to host tissues

  • key for biofilms
  • incr ability of bacteria to adhere to tissue → evade phagocytosis by PMNs
  • types of pili:
    1. type I pili
      • adhere to mannose receptors in urinary epithelial monosacch lining
      • bind to PMNs
      • major cause of cystitis
    2. type P pili
      • mannose-resistant
      • adhere to renal glycolipid receptors (DgalDgal residues) on renal epithelia
      • cause cystitis and pyelonephritis
    3. hemolysins
      • cytotoxic: form transmembrane pores in host cell membranes
    4. K antigens
      • promote bacterial virulence by decr ability of abs and/or complement to bind bacterial surface
      • K1 composed of polymer of n0acetyl neuraminic acid (antiphagocytic, works as an antigenic disguise)
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14
Q

asymptomatic bacteriuria

treat? or no?

A

no need for treatment in most cases

however, always treat:

  • pregnant women
  • prior to urologic surgery
  • hip replacement candidates (will have to undergo long catherization)

IF TREATING: tx based on results of urine culture and sensitivity

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15
Q

acute uncomplicated UTIs

A

sporadic, comm-acquired cases

present w typical sx: dysuria, freq, suprapubic pain

NO URINARY SX WITHIN LAST MONTH

micro:

  • urine cultures typically unnecessary
  • E. coli (75-95%), Enterocbacteriaceae (Proterus, mirabilis, Klebsiella pneumonia), Staph saphrophyticus
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16
Q

UTI treatment

A

antibiotics chosen for:

  • urinary excretion
  • low tox risk
  • high oral bioavailability
  • low cost

*IV tx preferred for complicated UTIs

meds:

  • trimethoprim-sulfamethoxazole
    • blocks folic acid synth → purine synth interrupted
  • nitrofurantoin
    • directly damages microbial DNA (bacteria metabolize toxic intermediates of nitrofurantoin more rapidly than human cells)
  • fosfomycin
    • inhibits bacterial cell wall biosynth by inactivating bacterial MurA (emzyme catalying peptidoglycan biosynth)
  • fluoroquinolones
    • inhibition of DNA gyrase, topo IV (req for DNA repl, transc)
    • try to avoid except in severe inf! bc of resistance emerging
17
Q

acute uncomplicated pyelonephritis

A

infection of kidney/upper urinary tract

  • general UTI sx (dysuria, freq, urg, suprapubic pain)
  • also…
    • fever
    • flank pain
    • CVA tenderness

believed to be “severe” if sx accompanied by n/v

same workup, same causative organisms

antibiotic choice: depends on outpatient/inpatient

  • outpatient: long acting parenteral antibiotics (ex. ceftriaxone), fluoroquinolones; trimethoprim-sulfamethoxazole, beta lactam (only if pathogen known)
  • inpatient: IV fluoroquinolones, aminoglycoside, ext spectrum cephalosporin, ext spectrum penicillin, carbapenem
18
Q

complicated UTIs

A

associated with structural or functional anormality or presence of underlying disease that..

  • incr risk of serious outcome
  • incr risk of failing initial therapy

bacterial spectrum considered much larger than uncomplicated UTIs

19
Q

complicated UTIs - treatment

A

E. coli still accounts for 75-95%, but in this set of UTIs, fluoroquinolone resistance more common and ESBL-producing E. coli (ext spectrum beta lactamase) more common

E. coli, Klebsiella, Staph sapro, as well as…

  • Pseudomonas
  • Serratia
  • Providencia
  • Enterococci
  • Staphylococci
  • fungi

use empiric antibiotics for longer periods of time:

  • oral fluoroquinolones
  • IV: ceftriaxone, ertapenem, aminoglycosides, vancomycin or ampicillin, antifungals
20
Q

catheter associated UTI

******

why so imp?

treatment

A

most common healthcare-assoc infection

leading cause of secondary hospital bacteremia

15-25% of pts are catheterized for 2-4d

  • 3-8% per day you have catheter get UTI
  • eventually all will develop bacteriuria as bacteria track up the catheter forming a biofilm or ascend through the lumen on the catheter

treatment: broad spectrum antibiotics for 10-14 days OR amphotericin if fungal, guided by urine culture results

  • often resistant to fluoroquinolones
  • need to remove catheter (can replace if necessary)
21
Q

complicated UTI

pregnancy

A

in pregnant women…

  • asymp bacteriuria: 2-7%
    • 30-40% of these → UTIs
    • associated with…
      • low birth weight
      • preterm birth
      • incr perinatal mortality
  • acute cystitis: 1-2%
  • pyelonephritis: 0.5-2%

often occrs in first trimester

linked to physiological changes in pregnancy:

  • sm muscle relaxation/ureteral dilatation
  • displ of ureter by enlarging uterus → stasis of urine
  • incr pressure on bladder from gravid uterus

ALL POSITIVE CULTURES → TREATMENT

  • redo culture in 1wk, 2wk, 1mo → might need
22
Q

complicated UTI

pregnancy

treatment

A

fluoroquinolones and trimethoprim-sulfamethoxazole are CONTRAINDICATED bc of teratogenicity!

  • TMP: folic acid antagonist → abnormal embryonic devpt in animals
  • sulfonamides: can displace bilirubin from pl binding sites and can increase kernicterus
  • fluoroquinolones: teratogenic in animal models
  • aminoglycosides: risk of fetal ototoxicity

cephalosporins, penicillins, aztrenam, carbapenems (except imipenem-cilastin), nitrofurantoin all ok

23
Q

UTI in children

risks of pyelonephritis

when to hospitalize

A

if proceeds to pyelonephritis…

  • renal scarring
  • HTN
  • impaired renal fx

hospitalize if:

  • under 2 months
  • clinical urosepsis
  • any immunocompromised child
  • vomiting/inability to take oral meds
  • failure to respond to tx
  • lack of adequate followup
    *
24
Q

vesicoureteral reflux

A

assoc with UTI in children

primary VUR: incompetent or inadequate closure of UVjx during bladder contraction

  • growth results in spontaneous resolution of low-grade VUR

secondary VUR: abnormally high bladder pressures result in incompetence of UVJ closure

  • assoc w anatomic abnormalities (posterior urethral valves)
  • functional bladder obstruction

genetics involved

25
Q

VUR dx

A

demonstration of reflux from bladder to urinary tract on imaging with voiding cystourethrogram (VCUG)

26
Q

prostatitis

A

affects young to middle-aged men

symptoms:

  • bladder irritation
  • outlet obstruction
  • blood in semen
  • painful ejaculation

pathophys: bacteria enter prostate via urine reflux from urethra/bladder through prostatic ducts

E. coli, Proteus spp, Klembiella/Enterobacter/Serratia, P. aerunginosa, S. aureus, Streptococci, Enterococci

27
Q

sterile pyuria

A

infectious and non-infectious causes

INFECTIOUS

  • genitourinary TB (27% of cases) - most common site after lungs, lymph nodes

NON-INFECTIOUS

anything that inflames the urinary tract

28
Q

UTI of transplated kidneys

A

all considered complicated bc patients are immunosuppressed

all cystitis is essentially pyelonephritis

  • short ureter
  • ALWAYS reflux through anastomosis of donor ureter to bladder
  • most kidney transplat centers place ureteric stents, which are removed in first months post transplant

almost always decr in kidney fx with episodes of cystitis

29
Q

summary1

A
30
Q

summary2

A
31
Q

summary3

A
32
Q

summary4

A

M2 Renal (12 decks)

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