Pyelonephritis & UTI

Definition: A renal disorder affecting the tubules, interstitium

& renal pelvis which can occur in two main forms:
o Acute Pyelonephritis
Caused by bacterial infection
Renal lesion associated with UTIs
o Chronic Pyelonephritis
Complex pathology involving bacterial infection +
other factors (e.g. obstruction, vesicoureteral
reflux)
Lower UTI, which can be completely asymptomatic
(asymptomatic bacteriuria) always carry the potential to
spread to the kidney!

Etiology
The dominant etiologic agents (>85% of cases) are G-ve
bacilli that normally inhabit intestinal tract:
o E. coli by far the most common
o Proteus
o Klebsiella
o Enterobacter
Other agents:
o Streptococcus faecalis (also enteric origin)
o Staphylococci
o Virtually every other bacterial & fungal agent
In immunocompromised persons (esp. transplant patients),
viruses can also cause renal infection:
o Polyamovirus
o CMV
o Adenovirus
Pathogenesis
In most patients with UTI, the infecting organisms are derived
from patients own fecal flora = Endogenous Infection
Two routes by which bacteria can reach kidneys:
o Haematogenous infection i.e. through bloodstream (less
common)
Results from seeding of the kidneys by bacteria
from distant foci in the course of septicemia or
infective endocarditis
Common agents:
Staph
E. coli
o Ascending infection i.e. from lower urinary tract (most
common)

More

likely to occur in:

Ureteral obstruction
Debilitated patients
Immunosuppressed patients
Infections with non-enteric organisms e.g.
staph, certain fungi & viruses
Common agents:
E. coli
Proteus
Enterobacter

Mechanism of Ascending Infection

Most common cause of clinical pyelonephritis

Normal human bladder & urine are sterile which is achieved
through a number of mechanisms these must fail for
ascending infection to occur
Pathogenic mechanism:
o Colonisation of distal urethra & introitus by coliform
bacteria
Depends on ability of bacteria to adhere to
urethral mucosal epithelial cells
Adhesins on P-fimbrae (pili) of E. coli
bacteria that are encoded by PAP gene,
interact with receptors on surface of
uroepithelial cells
Other types of fimbrae also impo. in renal tropism
& persistence of infection
o Ascent from urethra to bladder
This can be aided via instrumentation or
urethral catheterization (esp. if long term)
Urinary infections more common in females (f):
Shorter urethra in females
Absence of antibacterial properties of
prostatic fluid
Hormonal changes affecting bacterial
adherence to mucosa
Urethral trauma during sexual intercourse
o Urinary tract obstruction & stasis of urine
Impo. predisposing factor
Outflow obstruction/ Bladder dysfunction
incomplete emptying & increased residual volume
of urine stasis of urine bacteria introduced
into bladder can multiply w/o being
flushed/voided/destroyed
Can occur in:
BPPH

Tumours
Calculi
Neurogenic bladder e.g. diabetes, spinal
cord injury
o Vesicoureteral reflux
Incompetence of vesicoureteral valve is the critical
factor in allowing bacteria to ascend to the renal
pelvis
In the absence of this infection remains
localized to bladder
Vesicoureteral reflux is prevented by:
Ureteral insertion into bladder is a
competent one-way valve which prevents
retrograde flow of urine esp. during
micturition when intravesical pressure rises
Causes:
Congenital absence or shortening of
intravesical proteion of ureter
Acquired cause: Persistent bladder atony (f)
spinal cord injury
Bladder infection bacterial/inflammatory
products act on ureteral contractility
accentuate vesicoureteral reflux
Effect: Residual urine in urinary tract (ureters)
after voiding favours bacterial growth
o Intrarenal reflux
Open ducts at the tips of the papillae allow
residual urine in ureters to be propelled up to the
renal pelvis and deep renal parenchyma
This affects upper & lower poles of kidneys
compared to the midzones
In the poles, papillae tend to have flattened,
concave tips rather than convex pointed tips
present in midzones
Acute pyelonephritis
Definition: Acute suppurative inflammation of the kidney
caused by bacterial & sometimes viral (polyomavirus)
infection either via haematogenous seeding or ascending
infection
Morphology
o Hallmarks:
Patchy Interstitial Suppurative Inflammation can
appear as:
Discrete focal abscesses involving 1 or both
kidneys or

Extend to large wedge-shaped areas of

suppuration
Intratubular aggregates of neutrophils
In early stages, limited to interstitial tissue
Eventually, they infiltrate tubules & produce
abscesses with destruction of tubules
Glomeruli are relatively resistant to
infection (however, eventually they are
destroyed + fungal pyelonephritis affects
the glomeruli)
Tubular necrosis
o Three complications:
Papillary necrosis
Seen in diabetics & those with UT
obstruction
Usually bilateral (rarely unilateral)
Gray-white to yellow necrosis
Microscopic examination: Coagulative
necrosis with preservation of outlines of
tubules
Pyonephrosis
Total/near complete obstruction with pus
Suppurative exudate is unable to drain &
thus fills the renal pelvis, calyces & ureter
with pus
Perinephric abscess
Extension of suppurative inflammation
through renal capsule into perinephric tissue
o Healing following acute phase of pyelonephritis:
Neutrophilic infiltrate replaced by macrophages,
plasma cells, lymphocytes
The inflammatory foci are replaced by
irregular scars that can be seen on cortical
surface as fibrous depressions
The pyelonephritic scar is almost always
associated with inflammation, fibrosis, and
deformation of the underlying calyx and pelvis
Clinical features
o Predisposing conditions:
Urinary tract obstruction congenital/acquired
Instrumentation of urinary tract e.g.
catheterization
Vesicoureteral reflux
Pregnancy 4-6% develop bacteriuria during
pregnancy 20-40% eventually develop
symptomatic urinary infection if not treated

Gender & age Infections more common in female

between 1-40 yrs. But > 40 yrs, incidence in
males rises (f) BPPH and instrumentation and <1
yrs males have more congenital anomalies
Pre-existing renal lesions intrarenal scarring &
obstruction
Diabetes mellitus increased susceptibility to
infection + neurogenic bladder dysfunction +
more frequent instrumentation
Immunosuppression & Immunodeficiency
o Symptoms:
Sudden onset of pain at costovertebral angle
Systemic evidence of infection fever & malaise
Signs of bladder & urethral irritation dysuria,
frequency, urgency
o Investigation findings:
Pyuria but this does not differentiate upper &
lower UTIs
Leukocyte casts indicates renal involvement
Urinary culture establishes diagnosis of infection
o Clinical course:
Uncomplicated acute pyelonephritis follows a
benign course symptoms disappear within a few
days after giving antibiotic therapy
Some bacteria may persist or recur (f) new
serotypes of E. coli/other organisms
If untreated + urinary obstruction/diabetes
mellitus/immunodeficiency repeated
septicaemic episodes + papillary necrosis acute
renal failure
Polyomavirus nephropathy
o Pyelonephritis caused by polyomavirus in kidney
allografts
o Latent infection with polyomavirus is widespread in
general population, but immunosuppression of allograft
can lead to reactivation of latent infection
development of nephropathy allograft failure in 1-5%
of kidney transplant recipients
o Characterised by viral infection of tubular epithelial cell
nuclei nuclear enlargement & intranulcear inclusions
(composed of virions arrayed in distinctive crystallinelike lattices)

Chronic pyelonephritis & reflux nephropathy

Disorder in which chronic tubulointerstitial inflammation &
renal scarring are associated with pathologic involvement of
the calyces & pelvis

Pelvocalycael damage is .??????

Chronic pyelonephritis is an important cause of end-stage
kidney disease
Can be divided into 2 main forms:
o Chronic reflux-associated nephropathy
Most common form of chronic pyelonephritic
scarring
Renal involvement in reflux nephropathy occurs
early in childhood as a result of superimposition
of a urinary infection on congenital
vesicoureteral reflux and intrarenal reflux.
Reflux may be unilateral or bilateral; thus, the
resultant renal damage may cause scarring and
atrophy of one kidney or involve both, leading to
chronic renal insufficiency.
Vesicoureteral reflux occasionally causes renal
damage in the absence of infection (sterile reflux),
but only when obstruction is severe
o Chronic obstructive pyelonephritis
Recurrent infections superimposed on
diffuse or localized obstructive lesions lead to
recurrent bouts of renal inflammation and
scarring, resulting in a picture of chronic
pyelonephritis.
In this condition, the effects of obstruction
contribute to the parenchymal atrophy; indeed, it
is sometimes difficult to differentiate the effects of
bacterial infection from those of obstruction alone.
The disease can be bilateral, as with
posterior urethral valves, resulting in renal
insufficiency unless the anomaly is corrected, or
unilateral, such as occurs with calculi and
unilateral obstructive anomalies of the
ureter.
Morphology:
o Characteristic features include:
Irregularly scarred kidneys
Course, discrete, corticomedullary scars
overlying dilated, blunted, deformed calyces
& flattening of the papillae
The scars vary from one to several in number
Affect one or both kidneys irregularly
Most scars are in upper & lower poles of kidneys
Histology:
o Involve mainly the tubules & interstitium
o The tubules show atrophy in some areas &
hypertrophy/dilation in others

o Dilated tubules with flattend epithelium may be

filled with colloid casts = Thyroidization
o There are varying degrees of chronic interstitial
inflammation & fibrosis in the cortex & medulla
o In the presence of active infection neutrophils in
interstitium & pus casts in tubules
o Xanthogranulomatous pyelonephritis is an unusual and
relatively rare form of chronic pyelonephritis
characterized by accumulation of foamy macrophages
intermingled with plasma cells, lymphocytes,
polymorphonuclear leukocytes, and occasional giant
cells. Often associated with Proteus infections and
obstruction, the lesions sometimes produce large,
yellowish orange nodules that may be grossly confused
with renal cell carcinoma.
Clinical features:
o Onset of Chronic obstructive pyelonephritis may be:
Insidious/Silent
These patients come to attention relatively late (f)
gradual onset of renal insufficiency & hypertension
or (f) discovery of pyuria/bacteriuria on routine
examination
Acute, symptomatic
Acute recurrent pyelonephritis e.g. back pain,
fever, frequent pyuria,
Bacteriuria.
o Reflux nephropathy is often discovered when
hypertension in children is investigated.
Loss of tubular functionin particular of
concentrating abilitygives rise to polyuria and
nocturia.
Radiographic studies show asymmetrically
contracted kidneys with characteristic coarse
scars and blunting and deformity of the calyceal
system.
Significant bacteriuria may be present, but it is
often absent in the late stages.
o Although proteinuria is usually mild, some individuals
with pyelonephritic scars develop secondary focal
segmental glomerulosclerosis with significant
proteinuria, even in the nephrotic range, usually
several years after the scarring has occurred and often
in the absence of continued infection or persistent
vesicoureteral reflux. The appearance of proteinuria
and focal segmental glomerulosclerosis is a poor
prognostic sign, and patients with these findings may
proceed to chronic or end-stage renal failure. The
glomerulosclerosis, as we have discussed, may be

attributable to the adaptive glomerular alterations

secondary to loss of renal mass caused by
pyelonephritic scarring (renal ablation nephropathy).