Course: IDPT 5005
School of Medicine, University of Colorado at Denver, HSC
Francisco G. La Rosa, MD
URINARY TRACT INFECTIONS and TUBULOINTERSTITIAL DISEASES OF THE KIDNEY
I.
Learning Objectives:
A. Describe the pathogenesis of urinary tract infection in terms of routes of infection,
organism virulence factors, host defense mechanisms, predisposing factors, clinical
manifestations, and complications.
B.
Compare and contrast the features and pathogenesis of the two major causes of chronic
pyelonephritis (urinary tract obstruction and vesicoureteral reflux).
Note: Section on acute tubular necrosis in text (pp. 993-996) will not be covered in lecture or notes.
II.
Urinary Tract Infections (UTI) represent some of the most common infections in humans.
Although the vast majority of them remain confined to the lower urinary tract (bladder,
urethra), they may involve the upper urinary tract (ureter, pelvis, kidney) and have the
propensity to cause permanent kidney damage and even renal failure.
A.
B.
Routes of infection: ascending vs. blood borne.
1.
Ascending infection is the most common cause of UTI.
a.
Organisms which normally colonize the lower GI tract and perineal
skin become introduced into the urethral meatus and progressively
ascend to the urinary tract.
- colonization not enough to produce infection
- balance between organism virulence and host defenses (see
below)
b.
Coliform bacteria are the usual causative organisms
- E. coli most common ( 70%)
- Klebsiella, Proteus, Pseudomonas, Serratia, Strep species also,
especially in recurrent or hospital acquired infections
c.
E. coli only  1% of fecal flora
- Strain-specific virulence factors (see below) must therefore play a
role.
2.
Hematogenous infection is much less common.
a.
Occurs mainly in debilitated patients or in kidneys previously
damaged by some other process.
b.
Involves different organisms: S. aureus, group A strep
c.
Clinical setting: septicemia, endocarditis
Virulence factors
1.
Bacterial adhesion – certain strains of E. coli have “P” pili which allow for
attachment to glycosphingolipid receptors on urothelial cells. These so called
“uropathogenic” strains more commonly cause UTI, particularly
pyelonephritis. E. coli with P-pili agglutinate human RBCs (basis for test).
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C.
D.
2.
Persons with blood group P1 carry these uropathogenic strains more often
than those with blood group P2. They have a relative risk of recurrent
pyelonephritis that is eleven times that of the general population.
3.
Other bacterial antigens may offer resistance to host factors.
4.
Endotoxins produced by E. coli may inhibit ureteral peristalisis.
Host defense mechanisms
1.
Secretions of urethral glands
2.
Mucosal factors
3.
Hydrokinetic factors - urine flow
4.
Functional “valve” between bladder and ureter that prevents retrograde flow.
5.
Urine (poor culture medium).
Predisposing factors
Normally, host defenses are enough to oppose organism virulence and prevent
infection. Some predisposing factor may trip this balance and allow for UTI.
1.
Females more frequently affected than males:
a.
Shorter urethra
b.
Urethra more easily irritated (“honeymoon cystitis”)
c.
Vagina and introitus likely to be colonized by bacteria.
d.
Post-menopause: Lack of estrogen enhances colonization of vagina.
2.
Instrumentation
a.
Catheterization – especially indwelling catheters
b.
Cystoscopy
3.
Decreased urine flow/urinary stasis
a.
Urinary tract obstruction
b.
Incomplete voiding
c.
Infrequent micturition
d.
Low flow
e.
Bladder/ureteral diverticula
f.
Neurologic diseases affecting bladder control
4.
Calculi
a.
Cause obstruction
b.
Perpetuate infection – inhibit effectiveness of therapy
c.
Facilitate spread
5.
Vesico-ureteral reflux – backflow of urine from bladder to ureters, renal pelvis,
etc. (see below).
6.
Pregnancy (?)
7.
Diabetes (?)
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8.
E.
Other underlying diseases of kidney and urinary tract (e.g., polycystic
kidneys, congenital anomalies, vascular disease, etc).
Clinical manifestations
1.
Covert bacteriuria
a.
30:1 F:M
b.
15-20% have chronic pyelonephritis
c.
Scarring mostly occurs early in life (<age 4-5) probably due to reflux
with infection.
2.
Symptomatic UTI
For conceptual purposes, it is useful to categorize symptoms according to the
level to which micro-organisms have ascended and caused an inflammatory
reaction.
a.
Urethra and vesico-urethral valve:
- dysuria
- difficulty voiding
- incomplete emptying
- incontinence
b.
Bladder (cystitis)
- frequency
- suprapubic pain
c.
Ureters and kidneys (acute pyelonephritis)
- flank pain & tenderness-abdominal pain
- fever, chills
- oliguria
Note: For the individual patient, clinical data are not reliable indicators of the level of
infection.
3.
F.
Laboratory features
a.
Urinalysis: Many WBC’s, WBC casts (pyelonephritis), RBC’s
(variable).
b.
urine culture: usually > 100,000 bacteria/ml
always > 10,000 bacterial/ml
Complications of UTI
1.
Acute pyelonephritis – suppurative inflammation of the kidney and renal
pelvis caused by bacterial infection (less often fungal).
a.
Patchy, wedge-shaped regions of suppuration with microabscesses.
b.
Tubules filled with aggregates of PMNs
c.
Tubular destruction
d.
Interstitium – edema, PMNs, lymphs and plasma cells (may
predominate in areas away from abscesses or during resolution).
e.
Glomeruli preserved until late in course
f.
Papillary necrosis – especially in diabetics and obstructive
pyelonephritis.
2.
Perinephric abscess – usually an extension of acute pyelonephritis.
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III.
3.
Renal scarring.
4.
Recurrence.
5.
Stones - especially with Proteus infection.
Chronic pyelonephritis: There are two major circumstances that when combined with
chronic or recurrent infections are associated with renal scarring and progressive renal
impairment.
A.
Urinary tract obstruction
1.
Relationship between obstruction and infection
a.
Obstruction predisposes to infection (see above).
b.
Obstruction makes it difficult to eradicate infection and predisposes to
recurrence.
c.
Combination of obstruction and infection causes structural damage to
the kidney and urinary tract with loss of renal function (chronic
obstruction pyelonephritis). Probably a result of pressure-induced
ischemia and tubular atrophy combined with tissue injury from
organisms and inflammatory reaction.
2.
Causes of obstruction
a.
Intrinsic (intraluminal) masses of the urinary tract:
- exophytic tumors
- calculi
- sloughed necrotic papilla
- blood clots
b.
Inflammation, stricture of urethra or ureters
c.
Urethral valves
d.
Extrinsic compression:
- tumors (esp. pelvis, retroperitoneal)
- retroperitoneal fibrosis
- hemorrhage (trauma)
- iatrogenic (surgical ligation, adhesions)
e.
Functional:
- neurological disease
- diabetes mellitus
f.
Idiopathic
3.
Consequences of obstruction and infection (chronic obstructive
pyelonephritis)
a.
Structural changes – unilateral or bilateral depending on level of
obstruction.
- Dilatation of the urinary collecting system (hydroureter,
hydronephrosis).
- Atrophy and flattening of renal papillae and medulla: X-ray dx
- Fibrosis and atrophy of renal cortex.
- Microscopically:
o tubular atrophy
o fibrosis with patchy infiltration of lymphs & plasma cells
o focal edema and PMNs if superimposed acute infection
b.
Functional changes
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B.
Decreased GFR – irreversible after weeks to months
Hypertension
Vesico-ureteral reflux (VUR)
1.
Retrograde flow of urine from bladder into ureter and renal pelvis during
micturition.
a.
Although there is no anatomical valve at the ureterovesicle junction,
the oblique course of the ureter through the bladder wall forms an
effective “valve” in which the ureter is compressed during situations of
increased intravesicular pressure, especially during micturition.
b.
If the intramural segment of ureter is shortened or displaced such that
it enters the bladder perpendicularly, this functional valve is lost
allowing urine to reflux into ureter.
c.
VUR is most commonly apparent as an isolated abnormality in infancy
and decreases in frequency and severity throughout early childhood
(most resolved by age 5) – spontaneous remission.
- familial
- some cases may be associated with congenital malformations,
posterior urethral valves, neurogenic bladders, etc.
- renal scarring occurs early in life with little or no progression if
reflux abates (<5% progress to end-stage renal failure).
2.
Reflux nephropathy
The consequences of VUR include chronic or recurrent infections with nonobstructive pyelonephritis and renal scarring, termed reflux nephropathy. This
is usually associated with hypertension.
a.
VUR allows the pelvicaliceal system to be subjected to high pressure
during micturition, and allows organisms to gain access to the renal
parenchyma.
b.
Coarse, segmental scars lying directly over dilated calyces.
- Thinning of both cortex and medulla
- Often unilateral or unequally bilateral
c.
More extensive scarring at poles of kidney
- Related to papillae morphology – simple vs. compound papillae.
- Compound papillae have “open” ducts of Billini allowing for pelvictubular reflux.
- Compound papillae tend to be found at poles.
- Children without compound papillae resistant to renal scarring
d.
Small percentage of patients develops focal segmental
glomerulosclerosis.
C.
Recurrent infections without obstruction, reflux or some other underlying urinary tract
disease (e.g., stones, diabetes) rarely if ever cause chronic pyelonephritis.
REFERENCES
-
Chapters 20 & 21. Kumar, Robbins and Cotran: Pathologic Basis of Disease, 7th ed. WB
Saunders Co. Online: http://www.mdconsult.com/das/book/body/94286448-2/0/1249/0.html
Urological Pathology by William M. Murphy, Saunders, 2nd Edition, 1997, pp. 442-502
Urinary Tract Infections & Tubulointerstitial Diseases of the Kidney
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Disclaimers:
1. The primary goal of this chapter is to study the learning objectives outlined at the
beginning of this handout. The material to study is provided in the lectures, the handouts
and the recommended textbooks. All these sources provide the content over which you
will be tested. The lectures are intended to provide broad information of the material
found in the textbooks and handouts, and to give the students the opportunity to ask
questions on subjects not clear in the texts. The handouts do not seek to follow up the
sequence of the lectures, and most importantly, they are not a surrogate of the books.
2. The text presented in this handout has been edited by Dr. La Rosa from material found
in your books, from published articles and other educational works. This handout is
solely for educational purpose and not intended for commercial or pecuniary benefit (see
USA Copyright Law, Section 110, “Limitations on exclusive rights: Exemption of certain
performances and displays”). Reproduction and use of this handout can be done only
for educational use.
[Download] the USA Copyright Law version, October 2009.
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