Withey: Urinary Tract Infections Flashcards

1
Q

DEFINITION OF UTI BY LOCATION

Kidney:

A

Kidney: pyelonephritis

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2
Q

DEFINITION OF UTI BY LOCATION

Ureter:

A

Ureter: ureteritis

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3
Q

DEFINITION OF UTI BY LOCATION

Bladder:

A

Bladder: cystitis

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4
Q

DEFINITION OF UTI BY LOCATION

Prostate:

A

Prostate: prostatitis

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5
Q

DEFINITION OF UTI BY LOCATION

Urethra:

A

Urethra: urethritis

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6
Q

Lower UTI Definition: (3)

A

cystitis, prostatitis, urethritis

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7
Q

Presentation of Cystitis:

A

Cystitis: dysuria, urinary urgency and frequency, bladder fullness/discomfort; may also have hematuria

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8
Q

Presentation of Prostatitis:

A

Prostatitis: pain in lower back, perirectal area and testicles (as well as the above symptoms)

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9
Q

Upper UTI Definition: (3)

A

Upper UTI: pyelonephritis, intra-renal abscess, perinepheric abscess (late complication of pyelonephritis)

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10
Q

Why do women get UTIs?

A

A shorter urethra in women permits ascending infections of the bladder (cystitis).

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11
Q

Why do men get UTIs?

A

Physical abnormalities (such as enlarged prostate) may prevent voiding and enhance bacterial growth in the bladder.

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12
Q

Presentation of Pyelonephritis:

A

Pyelonephritis: cystitis symptoms as well as the following
o Fever/sweating
o N/V/D
o Flank pain
o Signs/symptoms of dehydration or hypotension
o Can show signs of speticemic shock

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13
Q

Uncomplicated UTI Definition:
Effect on long term renal function:
Duration:

A

Infection in a structurally and neurologically normal urinary tract

  • Little to no effect on long term renal function
  • Simple cystitis of short duration that is easily cleared with antibiotics
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14
Q

Complicated UTI Definition:
Duration:
Males:
Antibiotic resistant bacteria:

A

Infection in a urinary tract with functional or structural abnormalities (indwelling catheters, renal stones, enlarged prostate)

  • Causes cystitis of long duration or hemorrhagic cystitis
  • UTIs in males always considered complicated
  • Antibiotic resistant bacteria also fall into this category
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15
Q

What is the leading cause of both complicated and uncomplicated UTIs?

A

E.coli

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16
Q

What are the leading cause of uncomplicated UTIs? (2)

A

E.coli, S.saprophyticus

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17
Q

What are the leading cause of complicated UTIs? (5)

- Two leading causes?

A

*E.coli, *Enterococcus, P.aeruginosa, Klebsiella, Proteus (an many others)

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18
Q

General pathogenesis
Entry

What determines how far it ascends?
What is it often due to?

A

Entry: ascent from urethra (how far it ascends depends on virulence factors)

Often due to poor hygiene (inoculation from host flora) or sexual contact

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19
Q

What is the most important factor in pathogenesis?

A

Adherence to host epithelium

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20
Q

General pathogenesis
Adherence to host epithelium

Why do the organisms need organelles?

A

Negative charge on both bacteria and epithelial surfaces, and therefore, the bacteria need organelles to reach out and attach host cells, effectively overcoming repulsive forces

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21
Q

General pathogenesis
Adherence to host epithelium

Maximum repulsion zone:
Ideal distance:

A

10um is the maximum repulsion zone

15um is where they want to be

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22
Q

General pathogenesis
Adherence to host epithelium

Examples:
G-
G+

A

Adhesions, pili/fimbriae (Gram negatives) and polysaccharides (G positives)

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23
Q

Uropathogenic E.coli (UPEC)

Virulence Factors: (7)

A
  1. Pili/Fimbriae-Associated Adhesins
  2. Type 1 pili
  3. Type S Fimbriae (SfaI and SfaII):
  4. Afrimbrial Adhesins
  5. Toxins
  6. LPS (Endotoxin)
  7. K Antigen (Polysaccharide Capsule)
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24
Q

Uropathogenic E.coli (UPEC)
P Pili Associated with Pyelonephritis (PAP)

Binds to:
How can individuals be predisposed?
Blocking by mannose:

A

Binds to digalatoside receptor (glycosphingolipids/globobiose)
- Individuals can be predisposed to infection due to high density of these receptors

Mannose insensitive (binding not blocked by mannose)

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25
Uropathogenic E.coli (UPEC) P Pili Associated with Pyelonephritis (PAP) Causes what in labs? Binds what on RBCs? Helps resist what? Induces what for inflammation?
Causes hemagglutination in lab (binds P Ags on RBCs) Help resist phagocytosis Proflammatory (induce IL-6, IL-8 and PMN infiltration)
26
Uropathogenic E.coli (UPEC) Type 1 Pili Mannose: Does what to RBCs? What does the invertible promoter element allow it to do?
Binds to mannose (therefore mannose sensitive) in order to mediate binding to uroepithelium Agglutinates RBCs Invertible promoter element allows it to be turned on in the bladder and off in the kidney
27
Uropathogenic E.coli (UPEC) Type S Fimbriae (SfaI and SfaII) Binds to what on glycoproteins? Mannose: Does what to RBCs?
Binds to sialic acids on glycoproteins (therefore, mannose insensitive) Agglutinates RBCs
28
Uropathogenic E.coli (UPEC) Type S Fimbriae (SfaI and SfaII) Effect on kidney and bladder: Often associated with: (2)
Causes both cystitis and pyelonephritis Often associated with neonatal meningitis and bacteremia
29
Uropathogenic E.coli (UPEC) Afrimbrial Adhesins Recognizes: What aids in adhesion to uroepithelium? What else do they aid in?
Recognize Dr blood group Ags AfaD and AfaE aid in adhesion to uroepithelium and internalization (recurrent UTIs)
30
Uropathogenic E.coli (UPEC) Afrimbrial Adhesins What does Dr adhesion recognize? What does it aid in?
Dr adhesion recognizes basolateral surface integrins to aid in internalization (recurrent UTIs)
31
Uropathogenic E.coli (UPEC) | Toxins: (2)
Alpha hemolysin | Cytotoxic necrotizing factor type 1 (CNF-1)
32
Uropathogenic E.coli (UPEC) Alpha hemolysin Effect on RBCs: Effect on renal tubular cells: Effect in pyelonephritis:
Lyses RBCs (iron for growth) and renal tubular cells Mediates kidney damage in pyelonephritis
33
Uropathogenic E.coli (UPEC) Cytotoxic necrotizing factor type 1 (CNF-1) What % of EPEC strains? Kills what tissue? What are not as virulent?
~40% of EPEC strains Kills human bladder epithelium by apoptosis Mutants in CNF-1 are not as virulent
34
Uropathogenic E.coli (UPEC) LPS (Endotoxin) What type of cytokine release? Synergistic effect with:
Proinflammatory cytokine release (i.e. IL-8) Synergistic effect with P fimbrae
35
``` Uropathogenic E.coli (UPEC) K Antigen (Polysaccharide Capsule) ``` Composed of: Resistance to:
Composed of polysaccharides Anti-phagocytic/serum resistance
36
What causes causes 80-90% of CA-UTIs? What is the source?
Uropathogenic E.coli (UPEC) Host’s own intestinal flora or sexual partner’s flora
37
Uropathogenic E.coli (UPEC) Ascending Infection of Urethra What do E.coli bind to the urethra with?
E.coli bind to urethra using Type 1 fimbriae (not washed out)
38
Uropathogenic E.coli (UPEC) Ascending Infection of Urethra What do E.coli bind to the Bladder with?
Ascend further to bladder where they again bind using Type 1 fimbriae with FimH tip
39
Uropathogenic E.coli (UPEC) Ascending Infection of Urethra How do E.coli move up the ureter?
Move up ureter using flagellar motility
40
Uropathogenic E.coli (UPEC) Ascending Infection of Urethra What mediates binding in the kidney? How does it evade immune response?
Reach the kidney where P fimbriae with PagG tip mediate binding (antigen switch to evade immune response as well)
41
Uropathogenic E.coli (UPEC) | What contributes to cell damage?
Inflammatory response and toxins contribute to cell damage
42
Uropathogenic E.coli (UPEC) Examination of urine Gram stain: Shape: Look for what type of cell? What are the G+ rods adhering to epithelial cells?
Gram stain: look for Gram negative rods, RBC and WBC | - Note: Gram + rods adhering to epithelial cells are lactobacilli (normal flora)
43
Uropathogenic E.coli (UPEC) Examination of urine Blood agar plate: MacConkey: Cysteine-lactose-electrolyte deficient agar (CLED):
Blood agar plate: beta hemolysis and quantitation Selective Media: - MacConkey: lactose positive colonies (red/pink) - Cysteine-lactose-electrolyte deficient agar (CLED): yellow colones
44
Uropathogenic E.coli (UPEC) Examination of urine Indole Test: Oxidase test:
Indole Test: pink/purple | Oxidase test: negative
45
Uropathogenic E.coli (UPEC) Identification Need to differentiate between: BAP Contaminants/Normal Flora: Questionable/Repeat: Bacterial Infection:
Need to differentiate between infection and contamination: BAP: streaked with calibrated loop so that 1 colony= 100 CFU/ml - Contaminants/Normal Flora: less than 10,000 organisms per mL - Questionable/Repeat: 10,000-100,000 organisms per mL - Bacterial Infection: greater than 100,000 organisms per mL
46
Staphylococcus saprophyticus Virulence Factors: (4) Ubiquity of homolysin:
1. S.saprophyticus surface associated protein 2. Hemagglutinin/fibronectin-binding protein 3. Hemolysin: not in all uropathogenic strains 4. Urease
47
Staphylococcus saprophyticus G +/-? Causes inflammation of what? Rarely causes: M vs F?
Gram + cocci Urethritis and cystitis Rarely causes pyelonephritis More common in females than males
48
Staphylococcus saprophyticus Urease Hydrolyzes urea to give: Toxic to:
Hydrolyzes urea to give ammonium ions Toxic to bladder tissue
49
Staphylococcus saprophyticus Urease Effect on urine pH: What forms with chronic UTIs?
Raises pH of urine (promotes formation of kidney stones that can obstruct urinary tract) Struvite stones with chronic UTIs (magnesium ammonium phosphate)
50
Staphylococcus saprophyticus Causes: Rarely associated with: F vs M: Possible risk factors: (4)
Causes: urethritis and cystitis (rarely associated with pyelonephritis) More common in females ``` Possible Risk Factors: o Auto-infection (colon) o Sexual activity o Hormone flux at menstruation o Spermicide nonoxynol-9 ```
51
Staphylococcus saprophyticus Laboratory Identification G+/-? Shape: Grows on what type of plate? Doesn't grow on:
Shape: Gram positive cocci in clusters Growth: CNA agar (none of MAC, EMB or CLED)
52
Staphylococcus saprophyticus Laboratory Identification Cat +/-? Coag +/-? Novobiacin sensitive?
Biochemical: catalase positive, coagulase negative, novobiacin resistant
53
Klebsiella pneumoniae | Virulence Factors: (5)
Type 1 Fimbriae Type 3 Fimbriae Polysaccharide Capsule LPS Urease
54
Klebsiella pneumoniae Type 1 and 3 Fimbriae Mannose sensitivity:
Type 1 Fimbriae: mannose sensitive hemagglutinin | Type 3 Fimbriae: mannose-resistant hemagglutinin
55
Klebsiella pneumoniae Polysaccharide Capsule Layers: Phagocytic?
Polysaccharide Capsule: bilayered and anti-phagocytic
56
Klebsiella pneumoniae LPS What type of resistance? Mediated by what?
LPS: serum resistance (mediated by O antigen)
57
Klebsiella pneumoniae Urease What does it convert urea into? What does it form? What % of isolates produce urease?
Hydrolyzes urea to give ammonium ions (stone formation; almost 100% produce)
58
Klebsiella pneumoniae Laboratory Identification ``` G +/-? Shape Appearance Lac +/-? Hemolytic? ```
Shape: Gram negative rod Appearance: mucoid colonies (due to capsule) Growth: lactose positive on MAC, EMB and CLED; non-hemolytic on BAP
59
Proteus mirabilis | Virulence Factors: (4)
Adhesins: Flagella Urease HpmA Hemolysin
60
Proteus mirabilis Adhesins MR/P Hemagglutinin? Contributes to colonization of: Increases risk of:
MR/P (Mannose Resistant Proteus-like): - Hemagglutinin - Contributes to colonization of urinary tract - Increases risk of acute pyelonephritis
61
Proteus mirabilis Flagella Motility contributes to:
Highly motile (swarming motility; contributes to ascending infection from ureters to kidney)
62
Proteus mirabilis | Urease production causes:
Urease: STRONG producer of urease (rapidly causes stone formation)
63
Proteus mirabilis | What virulence factor is potent and cytotoxic for a variety of cells?
HpmA Hemolysin: potent and cytotoxic for a variety of cells
64
Proteus mirabilis Adhesins PMF Hemagglutinin? Contributes to colonization of:
PMF (Proteus miribalis fimbria): - Not a hemagglutinin - Contributes to colonization of the bladder (not the kidney)
65
Proteus mirabilis Site of colonization: Infection:
Site of colonization: colon Infection: most often seen in patients with underlying disease
66
Proteus mirabilis Laboratory Identification ``` G +/-? Shape Lac +/-? Hemolytic? Smell: ```
Shape: Gram negative rods Growth: lactose negative on MAC, EMB and CLED; hemolytic with swarming phenomenon on BAP Smell: highly urease positive and culture reeks of ammonia
67
Enterococcus spp | Virulence Factors: (3)
Aggregation Substance (Asa1) Cytolysin Sex Pheromones
68
``` Enterococcus spp Aggregation Substance (Asa1) ``` Facilitates: Adhesion to what type of eukaryotic cells?
Facilitates conjugal plasmid exchange between cells Adhesion to eukaryotic cells expressing integrins
69
Enterococcus spp Cytolysin Lysis what?
Lyses RBCs (iron for growth)
70
Enterococcus spp Sex Pheromones Normally function where? What type of chemoattractant?
Normally function in plasmid acquisition Triggers immune response as neutrophil chemoattractant
71
Enterococcus spp Site of colonization: More common in what population?
Site of colonization: colon Infection: more often seen in hospitalized patients with indwelling catheters
72
Enterococcus spp ``` G +/-? Shape Tolerant to: Bile esculin +/-? Cat +/-? ```
Shape: Gram positive cocci Growth: salt tolerant (will grown in 6.5% NaCl) Biochemical: bile esculin positive; catalase negative
73
Host Protective Mechanisms For UTIs: (5)
Normal flora: but urinary tract is normally sterile (only in the anterior urethra) Flushing action of urine Sloughing of the epithelium High osmolality, low pH: hard for bacteria to survive - Insignificant immune defense
74
Host Factors In Infection What receptors do uroepithelial cells have that bacteria recognize? What do women with recurrent UTIs have more of?
Uroepithelial receptors that bacteria recognize (mannose R) Women with recurrent UTIs tend to have more mannose receptors
75
Host Factors In Infection What blood groups are more prone to developing recurrent UTIs? What allows bacteria to migrate against the flow of urine?
Pk and P1 blood groups more prone to developing recurrent UTIs Blockage or other physiological malfunction (neurological disorder, pregnancy, diabetes etc.) in urinary tract allows bacteria to migrate against the flow of urine
76
E. coli example 1) Penis/urethra: 2) Bladder: 3) Ureter: 4) Kidney:
1) Penis/urethra: Type 1 fimbriae 2) Bladder: Type 1 fimbriae, FimH tip 3) Ureter: Flagellar motility is important 4) Kidney: P fimbriae, PapG tip, antigen switching to evade immune response