Pathophysiology of Urinary Tract
Obstruction
Jamie Bartley D.O.
PGY 3..almost 4
5/27/09
MSU-COM Metro Detroit Urology
Outline
• I. Background
• II. Pathophysiology and pathological
changes with urinary tract obstruction
• III. Patient work-up and management
• IV. Causes of urinary tract obstruction
Definitions
• Hydronephrosis- Dilation of the renal
pelvis or calyces
• Obstructive uropathy- functional or
anatomic obstruction of urine flow at
any level of the urinary tract
• Obstructive nephropathy- when
obstruction causes function or anatomic
renal damage
Prevalence
• 3.1% in autopsy series
• No gender differences until 20 years
– Females more common 20-60
– Males more common older than 60
• 2-2.5% of children at autopsy
Causes of Obstructive Nephropathy
•
•
Table 37-1 -- Possible Causes of Obstructive Nephropathy
•
Ureter
•
Bladder and Urethra
Renal-
– Congenital, Polycystic kidney, Renal cyst, Fibrous obstruction at ureteropelvic
junction, Peripelvic cyst, Aberrant vessel at ureteropelvic junction
– Neoplastic- Wilms' tumor, Renal cell carcinoma, Transitional cell carcinoma of the
renal pelvis, Multiple myeloma
– Inflammatory- Tuberculosis, Echinococcus Infection
– Metabolic- Calculi
– Miscellaneous- Sloughed papillae, Trauma, Renal artery aneurysm
– Congenital- Stricture, Ureterocele, Ureterovesical reflux, Ureteral valve, Ectopic
kidney, Retrocaval ureter, Prune-belly syndrome
– Neoplastic- Primary carcinoma of ureter, Metastatic carcinoma
– Inflammatory- Tuberculosis, Schistosomiasis, Abscess, Ureteritis cystica,
Endometriosis
– Miscellaneous- Retroperitoneal fibrosis, Pelvic lipomatosis, Aortic aneurysm, Radiation
therapy, Lymphocele, Trauma, Urinoma, Pregnancy
– Congenital- Posterior urethral valve, Phimosis, Urethral stricture, Hypospadias and
epispadias, Hydrocolpos
– Neoplastic- Bladder carcinoma, Prostate carcinoma, Carcinoma of urethra, Carcinoma
of penis
– Inflammatory- Prostatitis, Paraurethral abscess
– Miscellaneous-Benign prostatic hypertrophy, Neurogenic bladder
Global Renal Functional Changes
•
Obstruction can affect hemodynamic variables and GFR
•
GFR= Kf(PGC-PT-PGC)
–
–
Degree of affect depends on extent and severity of obstruction, whether UUO or BUO, and whether
it has been relieved or not
Need to understand in order to comprehend the relationships between changes in
renal hemodynamics and alterations in GFR during and after obstruction
Kf- flomerular ultrafiltration coeffecient related to the surface area
and permeability of the capillary membrane
PGC- glomerular capillary pressure. Influenced by renal plasma
flow and the resistance of the afferent and efferent arterioles
PT- Hydraulic pressure of fluid in the tubule
P- the oncotic pressure of the proteins in the glomerular capillary
and efferent arteriolar blood
•
RPF= (aortic pressure-renal venous pressure)
–
–
–
renal vascular resistance
Influences PGC
Constriction of the afferent arteriole will result in a decrease of PGC and GFR
An increase in efferent arteriolar resistance will increase PGC
Hemodynamic Changes with Unilateral
Ureteral Occlusion
• Triphasic pattern of renal blood flow
and ureteral pressure changes
– 1. RBF increases during the first 1-2 hours
and is accompanied by a high PT and
collecting system pressure
– 2. For another 3-4 hours, the pressures
remains elevated but the RBF begins to
decline
– 3. 5 hours after obstruction, further decline
in RBF occurs. A decrease in PT and
collecting system pressure also occurs
Triphasic pattern of UUO
Hemodynamic Changes with Unilateral
Ureteral Occlusion
• Alterations in flow dynamics within the kidney occur
dye to changes in the biochemical and hormonal
milieu regulating renal resistance
– Phase I- The increased PT is counterbalanced by an increase
in renal blood flow via net renal vasodilation, which limits
the fall of GFR
• PGE2, NO – Contribute to net renal vasodilation early in UUO
– Phase II and III- An increase in afferent arteriolar resistance
occurs causing a decrease RPF. A shift in RBF from the
outer cortex to the inner cortex also occurs all reducing GFR
• Angiotensin II, TXA2, Endothelin - mediators of the
preglomerular vasoconstriction during the 2nd and 3rd phase of
UUO
Hemodynamic Changes with Bilateral
Ureteral Occlusion
• Only a modest increase in RBF lasting 90 minutes
followed by a prolonged and profound decrease in RBF
that is even more than with UUO
• The intrarenal distribution of blood flow changes from
the inner to the outer cortex (opposite from UUO)
• Accumulation of vasoactive substances (ANP) in BUO
that contributes to preglomerular vasodilation and
postglomerular vasoconstriction
– With UUO, these substances would be excreted by the normal
kidney
• When obstruction is released, GFR and RBF remain
depressed due to persisent vasoconstriction of the
afferent arteriole
– The post-obstructive diuresis is much greater than with UUO
Summary of UUO and BUO
Partial Ureteral Occlusion
• Changes in renal hemodynamics and
tubular function are similar to complete
models of obstruction
– Develop more slowly
• Animal Studies- Difficult to imitate
partial obstruction
– 14 days- normal functional recovery
– 28 days- recover 31% of function
– 60 days- recovery 8% of function
Effects of Obstruction on Tubular Function
• Dysregulation of aquaporin water channels in the proximal
tubule, thin descending loop, and collecting tubule
– Lead to polyuria and impaired concentrating capacity
• Sodium Transport
– Decreased which leads to a role in the postobstructed kidney’s
impaired ability to concentrate and dilute urine
– Much greater sodium and water excretion after release of BUO than
UUO
• Thought to be due to the retention of Na, water, urea nitrogen and
increased ANP, all which stimulate a profound naturesis
• Potassium and phosphate excretions follow changes in
sodium
– Decreased with UUO
– Increased transiently with BUO in parallel with the massive diuresis
• Deficit in urinary acidification
• Magnesium excretion is increased after release of UUO or
BUO
• Changes in pepetide excretion mark renal damage
Cellular and Molecular Changes lead to
Fiborosis and Tubular Cell Death
• Obstruction leads to biochemical, immunologic,
hemodynamic, and functional changes of the kidney
• A cascade of events occur which lead to release of
angiotensin II, cytokines, and growth factors (TGF-B,
TNF-a, NFkB)
– Some mediators are produced directly from the renal tubular
and interstitial cells
– Others are generated by way of fibroblasts and macrophages
• Progressive and permanent changes to the kidney occur
– Tubulointerstitial fibrosis
– Tubular atrophy and apoptosis
– Interstitial inflammation
Pathologic Changes of Obstruction
(porcine model)
• Gross Pathologic Changes
– 42 hours- Dilation of the pelvis and ureter and
blunting of the papillary tips. Kidney also heavier
– 7days- Increased pelviureteric dilation and weight.
Parenchyma is edematous
– 21-28 days- External dimensions of kidneys are
similar but the cortex and medullary tissue is
diffusely thinned
– 6 weeks- Enlarged,cystic appearing, weighs less
than non-obstructed kidney
• Did not see such differences in partially obstructed
kidneys
Pathologic Changes of Obstruction
(porcine model)
• Microscopic Pathologic Findings
– 42 hours- Lymphatic dilation, interstitial edema,
tubular and glomerular preservation
– 7 days- Collecting duct and tubular dilation,
widening of Bowman’s space, tubular basement
membrane thickening, cell flattening
– 12 days- Papillary tip necrosis, regional tubular
destruction, inflammatory cell response
– 5-6 weeks- widespread glomeular collapse and
tubular atrophy, interstitial fibrosis, proliferation of
connective tissue in the collecting system
Compensatory Renal Growth
• Enlargement of the contralateral kidney
with unilateral hydronephrosis or renal
agenesis
• A reduction in compensatory growth
occurs with age
• An increase in the number of nephrons
or glomeruli does not occur, despite
enlargement
Renal Recovery after Obstruction
• Degree of obstruction, age of patient, and
baseline renal function affect chance of
recovery
– Two phases of recovery may occur
• Tubular function recovery
• GFR recovery
• Duration has a significant influence
– Full recovery of GFR seen with relief of acute
complete obstruction
– Longer periods of complete obstruction are
associated with diminished return of GFR
• DMSA scan is predicative of renal recovery
Now on to the Clinical Stuff…
Management of Patients with Obstruction
Diagnostic Imaging
• Renal US
–
–
–
–
Safe in pregnant and pediatric patients
Good initial screening test
No need for IV contrast
May have false negative in acute obstruction
(35%)
– Hydronephrosis= anatomic diagnosis
• Can have caliectasis or pelviectasis in an unobstructed
system
– Doppler- measures renal resistive index (RI), an
assessment of obstruction
• RI= (PSV-EDV)/PSV
– RI > 0.7 is suggestive elevated resistance to blood flow
suggesting obstructive uropathy
Diagnostic Imaging
• Excretory Urography
– Applies anatomic and
functional
information
– Limited use in
patients with renal
insufficiency
• Increased risk of
contrast-induced
nephropathy
– Cannot use in
patients with
contrast allergy
Diagnostic Imaging
• Retrograde
Pyelography
– Gives accurate details of
ureteral and collecting
system anatomy
– Good if renal
insufficiency or other
risks for contrast
– Loopogram- use for
evaluation of patients
with cutaneous
diversions
• Antegrade Pyelography
– Can do if RGP is not
possible and other
imaging doesn’t offer
enough details
Diagnostic Imaging
• Whitaker Test
– “True pressure” within the pelvis =
Collecting system pressure – intravesicle presure
• Saline or contrast though a percutaneous
needle or nephrostomy tube at a rate of 10mL/
min
• Catheter in bladder to monitor intravesicle
pressure
Normal < 15 cm H2O
Indeterminate = 15-22 cm H2O
Obstruction > 22 cm H2O
– Invasiveness and discordant results limit clinical usefulness
Diagnostic Imaging
• Nuclear Renography
– Provides functional assessment without contrast
• Obstruction is measured by the clearance curves
– Tc 99m DTPA- glomerular agent
– Tc 99m MAG3 – tubular agent
– Diuretic renogram- maximizes flow and
distinguishes true obstruction from dilated and
unobstructed
Normal = T ½ < 10 min Indeterminate = T ½ 10-20 min Obstructed T ½ > 20 min
Diagnostic Imaging
• CT
– Most accurate study to
diagnose ureteral calculi
– More sensitive to identify
cause of obstruction
– Helpul in surgical planning
– **Preferred initial imaging
study in those with suspected
ureteral obstruction
• MRI
– Can identify hydro but unable to
identify calculi and ureteral
anatomy of unobstructed
systems
– Diuretic MRU can demonstrate
obstruction
• Especially accurate with
strictures or congential
abnormalities
– IV gadopentetate-DTPA allows
functional assessment of
collecting system while providing
anatomic detail
• GFR assessment
• Renal clearance
– Still several limitations in its use
Issues in Patient Management
• Hypertension
– Can be caused by ureteral obstruction
• Especially BUO or obstruction of a solitary
kidney
• Less common with UUO
– Volume-mediated
• Increased ANP with obstruction which
normalizes after drainage
• Decreased plasma renin activity
Issues in Patient Management
• Renal Drainage
– Endourologic or IR procedures allow prompt temporary
and occasionally permanent drainage
• No statistically significant difference in HRQL between the two
techniques
• Patients with extrinsic compression causing obstruction have a
high risk of ureteral stent failure
–
–
–
–
42-56.4 % failure rate at 3 months
43% failed within 6 days of placement in one study
High failure rate at even getting placement(27%)
Stent diameter did not predict risk of failure
– Ultrasound guided percutaneous drainage should be
initial consideration in pregnant patients
– Percutaneous placement with suspected pyonephrosis
• Large diameter ureteral stents
Issues in Patient Management
Considerations in Surgical Intervention
• Reconstruction
– Endoscopic, open and laparoscopic techniques
should be considered
• Need for nephrectomy?
– Allow 6-8 weeks for adequate drainage
before proceeding
– Nuclear imaging provides accurate
functional information
• < 10% contribution to global renal function is
considered threshold for nephrectomy
Issues in Patient Management
Pain
• Increases in collecting system pressure and
ureteral wall tension contribute to renal colic
– Results in spinothalamic C-fiber excitation
• Treating Pain
– Narcotics
• Rapid onset, nausea, sedation, abuse
– NSAIDS
• Targets the inflammatory basis of pain by inhibiting
prostaglandin synthesis
• Reduces collecting system pressure by decreasing renal
blood flow
• Avoid in patients with renal insufficiency, GI bleeds
Issues in Patient Management
Postobstructive Diuresis
• Usually with BUO or solitary kidney
• Urine output > 200ml/hour
• A normal physiologic response to volume
expansion and solute accumulation
– Elimination of sodium, urea, and free water
– Diuresis ends when homeostasis returns
• Pathologic postobstructive diuresis
– Impaired concentating abilility or sodium
absorption
• Downregulation of sodium transporters and sodium
reabsorption in the thick ascending loop of Henle
• Increased production and altered regulation of ANP
• Poor response of collecting system to ADH
Issues in Patient Management
Postobstructive Diuresis
• Management
– Monitor those with BUO or UUO in solitary kidney for
POD
• Electrolytes, Mg, BUN, Cr
– Intensity of monitoring depends on clinical factors
• If no signs of POD If alert, no fluid overload, normal renal
function, normal lytes,  discharge and follow up
• If signs of POD  If alert, able to consume fluids, normal
VS continue in-patient observation, free access to oral
fluids, and daily labs until diuresis resolves (No IV Fluids)
• If signs of POD and signs of fluid overload, poor renal
function, hypovolemia, or MS changes Frequent VS and u.o
records, labs q 12 hrs (or more), urinary osmolarity, restrict
oral hydration (Minimal IV fluid hydration)
– Most have self-limiting physiologic diuresis
– If pathologic diuresis occurs- very intense monitoring is
indicated
Selected Causes of Extrinsic
Ureteral Obstruction
Retroperitonal Fibrosis
• Condition in which an inflammatory mass, a
fibrous whitish plaque, envelops and potentially
obstructs retroperitoneal structures
• Usually extends from the renal hilum to pelvic
brim
– May involve the mediastinum and the pelvis
• 2 phases lead to its development
1. Autoimmune reaction thought to occur due to leakage
of ceroid from the atheromatous plaques in the aorta
• Local inflammatory reaction characterized by plasma cells,
lymphocytes, macrophages, eosinophils
2. Fibrotic maturation with development of homogeneous
fibrous tissue with limited cellularity
Retroperitoneal Fibrosis
• 1: 200,000, 3:1 Male: Female,
• 2/3s of Cases are “Idiopathic”
Age 50
– 8-10% of cases have underlying malignancy
– Other causes: Medications (methysergide,
hydralazine, Haldol, B-Blockers, LSD, Phenacetin,
Amphetamines), RP hemorrhage, urinary
extravasation, trauma, radiation, IBD, Gonorrhea,
collagen disease, peri-aneurysmal inflammation
• Symptoms- Dull, non-colicky pain in a “girdle”
distribution, ureteral or vascular obstruction
(late)
Retroperitoneal Fibrosis
• Diagnosis
– IVP- Medial deviation of the ureters
• Can be seen in 18% of normal subjects
– CT – well demarcated mass that is
isodense with muscle (non-contrast study)
– MRI- Allows superior soft tissue
discrimination and can more accurately
distinguish the plaque from the great
vessels
Diagnosis of Retroperiteoneal Fibrosis
Retroperitoneal Fibrosis
•
Treatment
1. Correct obstructive uropathy
2. Biopsy to exclude malignancy
3. If biopsy is negative, medical therapy is preferred
–
–
–
–
Discontinue any offending medications
Corticosteroids- prednisolone 60mg qod x 2 mos, tapered to 5mg
daily over the next 2 months, then continue 5mg daily for 2 years
Tamoxifen
Experimental
Immunotherapy
4. Ureterolysis- if patient not a candidate for medical therapy or if
it fails
- May do open or laparoscopic
- Bilateral treatment is recommended even if unilateral
disease
- To prevent recurrent ureteral involvement bring ureter
intraperitoneal, or wrap in omentum
- Stents can usually be removed 6-8 wks after ureterolysis
Pelvic Lipomatosis
• Rare benign proliferative disease
involving the mature fatty tissues of the
pelvic retroperitoneum
• 18:1 Male to female
• More common in African American men
• Unknown etiology
– Obesity?
– Genetic?
Pelvic Lipomatosis
• Patient Presentation and Diagnosis
– LUTS, Constipation, non-specific pain, HTN
– Physical Exam- suprapubic mass, high
riding prostate, indistinct pelvic mass
– Younger patients are thought to have a
more progressive course than older
patients who have a more indolent course
Pelvic Lipomatosis
• Imaging
– KUB- Pelvic lucency
– IVP- Bladder is pear-shaped and elevated, hydronephrosis
may be evident
– CT- pelvic fat is readily demonstrated
Pelvic Lipomatosis
• Other evaluation
– Cystoscopy- cystitis cystica, cystitis glandular
(40%), adenocarcinoma, chronic UTI
• High bladder neck, pelvic fixation, and elongated
prostatic urethra may impair rigid cystoscopy
• Treatment
– Exploration is not recommended due to the
obliteration of normal planes and increased
vascularity of the mass
– In patients with obstructive uropathy stents,
PCNs, ureteral reimplanation, urinary diversion
Pregnancy
• Reported to occur in 43-100%
• Right > Left
• Etiology
– Hormonal- progesterone thought to
promote ureteral dilation
– Mechanical – increased degree of dilation
after 20 weeks when the uterus reaches
the pelvic brim
Pregnancy
• Diagnosis
– Usually asymptomatic
• If symptoms, may have flank pain or pyelonephritis
– US will show dilation to the pelvic brim
• If it extends below this, consider other etiologies (stone)
– Limited IVU or MRI to diagnose
• Treatment
– Most respond to conservative treatment
• IVF, analgesics, antibiotics
– If signs of sepsis or compromised renal function
may need ureteral stents or nephrostomy tubes
Endometriosis
• GU involvement
– Bladder 70-80%
– Ureter 15-20%
• May be intrinsic or extrinsic (80%)
• Cyclical flank pain, dysuria, urgency, UTI,
hematuria, or no GU symptoms (silent loss of
renal function may occur)
– Recommended to image the Upper tracts in all
patients with pelvic endometriosis (RUS or EXU)
Endometriosis
• Treatment
– Hormone therapy- if normal renal function
with mild hydro and no functional
obstruction seen on renogram
• GnRH agonists
– Surgery- treatment of choice for patients
with significant disease
• TAH with BSO
• Unilateral oopherectomy
• Ureterolysis if extrinsic disease
• Distal ureterectomy with reimplantation
Vascular Causes of Ureteral Obstruction
• Abdominal Aortic Aneurysm
– Ureteral obstruction may be the first sign
– Medial deviation of the ureters associated
with the desmoplastic reaction of
inflammatory AAA (IAAA) more likely to
cause obstruction than lateral deviation
– Stent placement usually recommended
prior to aneurysmal repair
• Ureterolysis usually not needed and obstruction
resolves with correction of the aneurysm
Circumcaval Ureter
• Anomalous course of the ureter to the
IVC leading to extrinsic obstruction
• Thought to be due to the persistence of
the subcardinal vein as the infrarenal
IVC, causing medial migration and
compression of the right ureter
– Other theories involve persistence of the
posterior cardinal vein as the infrarenal
cava
– Both, theories note failure of the
supracardinal vein to develop into the
infrarenal IVC
Circumcaval Ureter
Circumcaval Ureter
• Treatment is performed only in
presence of obstruction
– Divide ureter proximally and at the distal
point it emerges lateral to the IVC
– Spatulated ureterostomy performed
Other causes of vascular obstruction
• Iliac Artery Aneurysm
– Typically place internal ureteral stents prior to
aneurysmal repair
• Obstruction after Vascular Graft placement
– Usually resolves spontaneously
– Graft transection and repositioning
– Chronic stenting
• Puerperal Ovarian Vein Thrombophlebitis
– Antiobiotic therapy usually resolves