PATHOPHYSIOLOGY AND

MANAGEMENT OF UPPER
URINARY TRACT OBSTRUCTION
BABALOLA R N
SENIOR REGISTRAR,
UROLOGY UNIT, OAUTHC, ILE-IFE.
OUTLINE
INTRODUCTION
EPIDEMIOLOGY
AETIOLOGY
PATHOPHYSIOLOGY
CLINICAL FEATURES
DIAGNOSIS
TREATMENT
CONCLUSION
INTRODUCTION
Obstruction to the upper urinary tract, affecting the ureters, renal
pelvis and parenchyma
Could be acute or chronic, complete or incomplete, unilateral or
bilateral
Can result in sequelae like upper tract dilatation, impairment in renal
function, secondary hypertension as well as urinary tract infections
Prompt diagnosis and treatment is needed to preserve renal function
and improve quality of life
EPIDEMIOLOGY
A frequently encountered diagnosis in urology.
However, because of the fact its etiology is varied, reliable cumulative
incidence rates do not exist.
Antenatally hydronephrosis id detectable via ultrasonography and its
incidence is reported to be around 1%
The major cause in adults - intrinsic, intraluminal nephrolithiasis and
urolithiasis
CLASSIFICATION
Congenital vs acquired
Intraluminal vs extrinsic
Proximal vs distal
Unilateral vs bilateral(incl. solitary kidney)
AETIOLOGY
PATHOPHYSIOLOGY
EFFECT OF URETERIC OBSTRUCTION ON
URETERIC FUNCTION
Normal Pyelo-ureteric Peristalsis
Mechanisms poorly understood
During low urine output, renal pelvic contractions outnumber ureteric
contraction
During diuresis, renal pelvis contractility instigates myogenic transfer
of action potentials to the ureteric muscularis, leading to coordinated
pelvic/ureteric contractions
It is currently believed that the primary oscillator of ureteric
peristalsis is renal pelvic urine volume and its effect on pyelo-ureteric
pacemaker activity
 Pacemaker coordination of pyelourteric peristalsis has been
suggested to depend primarily on the activity of atypical smooth
muscle cells and interstitial cells of Cajal-like cells which predominate
in the renal pelvis, have a low depolarization threshold and act to
drive depolarization (and peristalsis) in naturally more refractory
typical smooth muscle cells
OBSTRUCTIVE NEPHROPATHY
Animal models
With complete obstruction comes associated urinary pooling which,
in combination with changes in ureteric contractility, gives rise to
retrograde pressure transfer to the proximal kidney and
hydronephrosis
With increasing time post obstruction, the kidney becomes swollen
because of pooling of urine proximal to the site of obstruction. As the
renal pelvis expands, the renal parenchyma becomes affected.
Flattening of the renal papilla and back filling of the collecting system
occurs. This leads to compression of the renal cortex causing the
characteristic cortical thinning observed in obstruction
Unilateral obstruction:triphasic
Renal blood Collecting system Comment
flow pressure
1 Afferent arteriolar
0 90 min
vasodilation

(6.5 to 70 mmHg)
2 Afferent and
90 min 5h
Efferent arteriolar

(by 40 70%) vasoconstriction
(remains elevated)
3 Collecting system
5 18h
dilatation

Pyelotubular
reflux
(continued (towards resting)
Pyelovenous reflux
decrease)
Pyelolymphatic
reflux
UNILATERAL UUO
Phase I (0-90 mins).
Pre-glomerular vasodilatation
Increased RBF in response to increased ureteral pressure.
Phases II and III
Post-glomerular vasoconstriction, then pre- and post-glomerular
vasoconstriction
Phase II (90 mins 4/5 hours) characterised by a fall in RBF with a
continued rise in ureteral pressure. Due to post-glomerular
vasoconstriction. Further attempt by kidney to maintain GFR.
 UNILATERAL UUO
Phase III (5 hours+)
Drop in RBF and ureteral pressure.
By 24 hours tubular pressure and ureteral pressure fall to 30% and
50% of control values respectively.
Vaso-constrictive mediators in Phase II and III:
o Eicosanoids, TXA2 and TXB2, Renin/ Angiotensin II
 Decreased GFR due to
Reduced single-nephron renal blood flow and
Shunting of blood from outer to inner cortex, decreasing the total number of
perfused glomeruli.
Mechanism of shunting. Increased production of renin witnessed in outer vs.
inner cortex.
Fall in ureteral pressure due to;
Reduced GFR
Pelvicalyceal dilatation
Pyelolymphatic and pyelovenous backflow
Unilateral obstruction
The contralateral kidney
Compensatory Growth
Response proportional to degree of injury
Initial vasoconstriction, subsequent vasodilation
Hypertrophy
Increased blood flow and GFR
Compensatory growth is age dependent
The number of nephrons remains constant
Increase in proximal tubular length due to increase
in cell size
Bilateral obstruction
Similar to unilateral upper tract obstruction
Less pronounced rise in blood flow initially
Less afferent vasodilation
Lasts 90 mins
More substantial decline in blood flow
Greater vasoconstriction (thought to be due to no renal
clearance of vasoconstrictors from other kidney)
Renal pelvic and ureteric pressures remain raised
for longer, approaching pre-obstruction pressure
at 24 hrs
No other side to compensate
Macroscopic effects on kidney
Dilatation of pelvis/calyxes hydronephrosis
Dilation of ureter
Flattened papillae (42hrs)
Parenchymal oedema (7 days)
Cortical parenchymal thinning (21 days)
Microscopic effects
42 hrs lymphatic dilatation, interstitial oedema

7 days collecting duct, tubular dilation, widening of

Bowmans space, tubular basement membrane thickening

9 days papillary tip necrosis and inflammatory cell

infiltrate

16 days interstitial fibrosis

3 weeks tubular loss, fibroblast growth, collagen

deposition

6 weeks Widespread tubular atrophy and fibrosis

Apoptosis is the principle mechanism of cell loss

Effect on tubular function
Down-regulation of aquaporin channels impairs concentrating
ability
Some down-regulation of active sodium transporters. In
addition fluid overload stimulates ANP secretion encouraging
natriuresis
Reduction in GFR and down-regulation of Na+/K+ ATPase
transporters reduces K+ excretion
Down-regulation of active H+ transporters results in a relative
failure of H+ ion excretion
In unilateral obstruction the other kidney can compensate
 Renal tubular swelling extends to the more proximal portions of the
nephron where flattening of the tubular epithelium can be observed.
These mechanical changes - renal tubular cell stress, which is
associated with increased oxidative stress, the induction of cell death
by apoptosis, and the initiation of both pro-inflammatory and
profibrotic signaling
The result of sustained UUO is therefore progressive tubular atrophy
accompanied by the development of tubulointerstitial fibrosis.
Following UUO there is relative preservation of renal microvascular
structure and glomerulosclerosis
Tubular Function in Bilateral Ureteric
Obstruction
Similar tubular defects as seen in UUO, but exacerbated due to
activity of ANP
Marked post-obstructive diuresis and natriuresis may be seen
Urine
Significantly increased total excretion of filtered load
Low osmolality
Normal/ High pH
High sodium content
High potassium content
 Return of renal function
Degree function return difficult to predict, relates to
degree of obstruction, duration and prior function
Dog experiments have been carried out:
7 days: full functional recovery
14 days: 70% recovery
28days: 30% recovery
6 weeks: no functional recovery
In humans return of function has been noted after 150
days
Difficult to predict
2 phases of recovery:
First 2 weeks recovery in tubular function
Next 10 weeks recovery in GFR
Post-obstructive diuresis
After release of bilateral urinary obstruction or obstructed solitary
kidney
Typically normal physiological response to accumulated fluid and
electrolytes. Once free water and solute excess resolves, diuresis
resolves
Most patients only require access to oral fluid and regular monitoring
(vital signs, hourly urine output, daily weight and daily U+E and Mg)
Pathophysiology
Progressive reduction in the medullary concentration gradient
secondary to vascular washout
Down-regulation of sodium transporters in the thick ascending loop
of Henle;
Reduction in glomerular filtration rate, which leads to ischemia and
loss of juxtamedullary nephrons;
Reduced response of the collecting duct to circulating antidiuretic
hormone, leading to nephrogenic diabetes insipidus
Post obstructive diuresis
Physiologic POD is self-limiting and generally lasts 24 hours.
Pathologic POD generally lasts longer than 48 hours and can be
exacerbated with excessive intravenous fluid replacement.
Studies from North West have shown that a UO > 20mml/h for >= 6
hours increases the likelihood of a pathological diuresis. IV fluids
should be administered if there are signs of hypotension or impaired
cognition
Post-obstructive diuresis
A simple method to estimate urine osmolality is to assess the urine
specific gravity.
A specific gravity of 1.010 is iso-osmotic with serum osmolality,
indicating that the kidneys do not need to concentrate the urine. This
is consistent with physiologic POD and is generally self-limiting.
A specific gravity of 1.020 demonstrates that the kidneys are
concentrating the urine and POD has resolved or has nearly resolved.
However, a specific gravity of 1.000 is hypo-osmotic with serum
osmolality, indicating the kidneys inability to concentrate the urine.
This is consistent with pathologic salt-wasting POD
Post-obstructive diuresis
Patients with pathologic POD require strict monitoring of vital signs,
fluid status, and serum electrolyte levels, and benefit from the
involvement of a nephrologist.
The type and amount of fluid should be tailored to the patients
needs based on his or her serum and urinary electrolyte levels and
clinical hydration status.
A practical recommendation is to replace 75% of the previous 1-hour
urinary output- 0.45% normal saline intravenously
CLINICAL PRESENTATION
Presentation of upper urinary tract obstruction is not homogeneous,
reflecting differences in etiology and degree of obstruction.
Antenatal obstruction presents during routine imaging.
In postnatal (including adult) obstruction, clinical presentation
depends on the whether the obstruction is unilateral or bilateral,
acute or chronic and partial or complete.
Presentation could be asymptomatic, detected on routine imaging; or
may be symptomatic
CLINICAL PRESENTATION
Symptomatic
Pain flank, suprapubic, colicky, radiating
Flank swelling
Urosepsis - Fever, chills, rigors, hypotension, altered sensorium
Weight loss
Other features depending on the specific cause pregnancy, pelvic
malignancies
Exam
General physical exam
Abdominal tenderness; lumbar mass; kidneys ballotable
 Imaging for obstruction
USS
Antenatal and post-natal
Can show dilatation (ie hydronephrosis)
False +ve
Excess flow eg Diuresis
Anatomy eg Extrarenal pelvis, Cysts
False ve
Too little flow eg dehydration
Operator dependent
Can use Doppler renal resistive index
>0.7 suggests obstruction, ~0.6 normal
(Peak systolic velocity-peak diastolic velocity) / Peak systolic velocity
Imaging for obstruction
IVU
Dynamic test
Functional information
Complete vs partial
Level of obstruction
Time consuming in
obstructed patients
 Imaging for obstruction
CT with or without
contrast
Quick
Good at identifying
causes both intrinsic and
extrinsic
Comparatively high
radiation dose
Imaging for obstruction

MRI
Can identify
hydronephrosis
No radiation
Useful in the pregnant
patient
Imaging for obstruction
Renogram
A study of the uptake, transit and elimination by the
kidney of an intravenous dose of a radionucleotide
Gives drainage and relative function
Limited anatomical information
Use of diuretic improves discrimination between
obstructed and non-obstructed
Renography

3 phases
DOSE %
Vascular phase,
1 2 3 represents uptake
12 Transit phase, represents
Renal transit through kidney
Elimination phase,
8 Bladder
excretion from the
kidney and expulsion
4
down the ureter

TIME (minutes)
0
10 20 30
 131I-Hippuran

Used in the 1960s

Hippuran is an excellent renography agent very
rapidly cleared by tubular secretion and some
filtration
131I emits around 90% of its radiation as beta decay,

which damages local tissue but doesnt penetrate far

enough to be detected
123I-Hippuran

All gamma decay

Half life of 13 hrs and needs a cyclotron to produce
Very expensive
 99mTc- DTPA
Cleared by filtration
Slow rate of clearance
High background signal
99mTc produced from a Mo-99 generator
99mTc-MAG-3
Rapidly cleared by tubular secretion and some filtration
(although 60% slower than Hippuran)
Low background signal
99mTc-DMSA
Used for renal scans for scars
Fixes in tubules function, not drainage
 Whittakers test
A test to help differentiate in those
with equivocal obstruction or poor
function where renogram unhelpful
Quite invasive, no more commonly
done
Nephrostomy in affected kidney
Catheterise
Patient prone in fluoroscopy
Infuse contrast/saline via
nephrostomy at 10mls/min
Measure pressure in kidney and
bladder and subtract to get the
difference
<15 cm H20 unobstructed
15-22 cm H20 equivocal
>22 cm H20 - obstructed
OTHER INVESTIGATIONS
Voiding cystourethrogram VUR, PUV
Urethrocystoscopy bladder neck, urethra; bilateral obstruction
Uretero-renoscopy ureteral strictures, valves
E/U/Cr
FBC
Urine MCS
Urinalysis
TREATMENT
GOALS
Preservation of renal function
Elimination of infection and obstruction
Depends on
The cause of obstruction
Presentation symptomatic vs asymptomatic
Overall/differential renal function
Presence of complications
Resuscitate, then treat
Available equipment
Available expertise
PROGNOSIS
Depends on
The cause
Antenatal vs post-natal detection
Presence or absence of antenatal renal hypoplasia/dysplasia
Renal function
Presence or absence of complications
CONCLUSION

Upper urinary tract obstruction is a frequently encountered diagnosis

in urology

Prompt detection of the cause, adequate management of possible

complications, and primary management of the cause is needed to

preserve or improve renal function

THANK YOU