Pathophysiology of Urinary Tract Obstruction

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Pathophysiology of Urinary Tract Obstruction

• Jamie Bartley D.O.
• PGY 3..almost 4
• 5/27/09
• MSU-COM Metro Detroit Urology

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Outline

• I. Background
• II. Pathophysiology and pathological changes with
  urinary tract obstruction
• III. Patient work-up and management
• IV. Causes of urinary tract obstruction

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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

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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

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Causes of Obstructive Nephropathy

• Table 37-1   -- Possible Causes of Obstructive
  Nephropathy
• 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
• Ureter
• 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
• Bladder and Urethra
• 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

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Global Renal Functional Changes

• Obstruction can affect hemodynamic variables and
  GFR
• Degree of affect depends on extent and severity
  of obstruction, whether UUO or BUO, and whether
  it has been relieved or not
• GFR Kf(PGC-PT-PGC)
• Need to understand in order to comprehend the
  relationships between changes in renal
  hemodynamics and alterations in GFR during and
  after obstruction
• 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

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
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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

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Triphasic pattern of UUO
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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

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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

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Summary of UUO and BUO
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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

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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 kidneys 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

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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

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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

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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 Bowmans 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

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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

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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

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Now on to the Clinical Stuff
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Management of Patients with ObstructionDiagnostic
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 gt 0.7 is suggestive elevated resistance to
  blood flow suggesting obstructive uropathy

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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

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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
  doesnt offer enough details

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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
• Invasiveness and discordant results limit
  clinical usefulness

Normal lt 15 cm H2O Indeterminate 15-22 cm
H2O Obstruction gt 22 cm H2O
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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 lt 10 min Indeterminate T ½ 10-20
min Obstructed T ½ gt 20 min
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Diagnostic Imaging

• 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

• 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

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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

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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

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Issues in Patient ManagementConsiderations 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
• lt 10 contribution to global renal function is
  considered threshold for nephrectomy

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Issues in Patient ManagementPain

• 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

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Issues in Patient ManagementPostobstructive
Diuresis

• Usually with BUO or solitary kidney
• Urine output gt 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

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Issues in Patient ManagementPostobstructive
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

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Selected Causes of Extrinsic Ureteral Obstruction
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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

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Retroperitoneal Fibrosis

• 1 200,000, 31 Male Female, Age 50
• 2/3s of Cases are Idiopathic
• 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)

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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

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Diagnosis of Retroperiteoneal Fibrosis
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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
• 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

Experimental
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Pelvic Lipomatosis

• Rare benign proliferative disease involving the
  mature fatty tissues of the pelvic
  retroperitoneum
• 181 Male to female
• More common in African American men
• Unknown etiology
• Obesity?
• Genetic?

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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

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Pelvic Lipomatosis

• Imaging
• KUB- Pelvic lucency
• IVP- Bladder is pear-shaped and elevated,
  hydronephrosis may be evident
• CT- pelvic fat is readily demonstrated

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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

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Pregnancy

• Reported to occur in 43-100
• Right gt Left
• Etiology
• Hormonal- progesterone thought to promote
  ureteral dilation
• Mechanical increased degree of dilation after
  20 weeks when the uterus reaches the pelvic brim

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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

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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)

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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

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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

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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

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Circumcaval Ureter
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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

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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